Process for producing organotitanium compound and process for addition reaction

ABSTRACT

A process for producing an organotitanium compound capable of regioselectively converting a substituted acetylene compound into polysubstituted benzene or polysubstituted pyridine. The process comprises reacting an acetylene compound represented by the formula (1) 
                         
[where R 1  and R 2  denote a C 1-20  alkyl group or the like] in the presence of a prescribed titanium compound and a Grignard reagent with a compound represented by the formula (4)
 
                         
[where R 3  and R 4  denote a hydrogen atom or the like] and further reacting with a compound represented by the formula (5)
 
                         
[where R 5  denotes a hydrogen atom or the like, Z denotes CR′ (where R′ denotes a hydrogen atom or the like), nitrogen atom, X 6  denotes a halogen atom or the like, and m is 0 or 1]
 
thereby giving the titanium compound represented by the formula (6) and/or (7).
 
                         
[where R 1 ˜R 5 , Z, X 6 , and m are defined as above; and X p  and X q  denote any of X 1 ˜X 4 ].

This application is a Divisional of application Ser. No. 10/013,453,filed on Dec. 13, 2001 now U.S. Pat. No. 6,743,916, the entire contentsof which are hereby incorporated by reference and for which priority isclaimed under 35 U.S.C. § 120; and this application claims priority ofApplication No. 2001-182554 filed in Japan on Jun. 15, 2001 under 35U.S.C. § 119.

BACKGROUND OF THE INVENTION

The present invention relates to a process for producing anorganotitanium compound useful for production of pharmaceuticals andagricultural chemicals and their intermediates and also to a process foraddition reaction involving the organotitanium compound. Moreparticularly, the present invention relates to a process for producingan organotitanium compound useful for production of polysubstitutedbenzene or polysubstituted pyridine.

There is an established process known as Reppe reaction for producing abenzene compound directly from three acetylene compounds in the presenceof a catalyst of transition metal catalyst. This reaction, however, hasdifficulty in producing a polysubstituted benzene compoundregioselectively from substituted acetylene compounds.

As for regioselective production of a substituted benzene compound fromthree acetylene compounds, several processes are disclosed in Chem. Rev.2000, 100, 2901–2915. These processes are based on condensation of onemolecule of diyne compound and one molecule of acetylene compound.Nothing is mentioned about the process of producing a substitutedbenzene compound regioselectively from three molecules of acetylenecompound.

There is known a process for producing a pyridine compoundregioselectively from two acetylene compounds and one nitrile compound.(J. Chem. Soc., Dalton 1978, 1278–1282, J. Am. Chem. Soc. 2000, 122,4994–4995)

The process disclosed in the former literature has the disadvantage ofrequiring an expensive cobalt complex and being incapable of using twoacetylene compounds of different kind. The process disclosed in thelatter literature has the disadvantage of requiring an expensivezirconium catalyst and also requiring two-stage reactions with differentcatalysts. Therefore, both processes are not suitable for industrialproduction.

SUMMARY OF THE INVENTION

The present invention was completed in view of the foregoing.Accordingly, it is an object of the present invention to provide aprocess for producing an organotitanium compound capable ofregioselectively converting a substituted acetylene compound into apolysubstituted benzene compound or a polysubstituted pyridine compound.It is another object of the present invention to provide a process foraddition reaction to produce polysubstituted benzene and polysubstitutedpyridine through addition of an electrophilic reagent to theorganotitanium compound.

In order to achieve the above-mentioned object, the present inventorscarried out extensive studies, which led to the finding that it ispossible to produce an organotitanium compound from a titanium reagentas a reaction product of a tetravalent titanium compound (which iscommercially inexpensive) and a Grignard reagent, the organotitaniumcompound being capable of converting three molecules of acetylenecompound, or one molecule of acetylene compound and one molecule ofdiyne compound, into a benzene compound regioselectively, or convertingtwo molecules of acetylene compound and one molecule of nitrile compoundinto a pyridine compound regioselectively. The present invention isbased on this finding.

The present invention provides the following.

-   [1] A process for producing an organotitanium compound which    comprises reacting an acetylene compound represented by the    formula (1) below in the presence of a titanium compound represented    by the formula (2) below and a Grignard reagent represented by the    formula (3) below with an acetylene compound represented by the    formula (4) below and further reacting with a compound represented    by the formula (5) below, thereby giving the titanium compound    represented by the formula (6) and/or (7) below.

[where R¹ and R² denote mutually independently a C₁₋₂₀ alkyl group{which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkylaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆ alkyl groupor phenyl group), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denotemutually independently a halogen atom, C₁₋₆ alkyl group, or phenylgroup).]TiX¹X²X³X⁴  (2)[where X¹, X², X³, and X⁴ denote mutually independently a halogen atom,C₁₋₆ alkoxy group {which may be substituted with a phenyl group (whichmay be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup) or naphthyl group}, phenoxy group (which may be substituted witha C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenoxy group), or naphthoxygroup.]RMgX⁵  (3)[where R denotes a C₂₋₈ alkyl group having a hydrogen atom at the βposition, and X⁵ denotes a halogen atom.]

[where R³ and R⁴ denote mutually independently a hydrogen atom, C₁₋₂₀alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkylaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹R¹² (where R¹⁰,R¹¹, and R¹² are defined as above).]

[where R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group) or naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ group {where R⁶ denotes a C₁₋₆ alkylgroup or phenyl group (which may be substituted with a halogen atom orC₁₋₆ alkyl group) and n denotes 1 or 2}, OSO₂R⁶ group (where R⁶ isdefined as above), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkylgroup); and m denotes 0 or 1.]

[where R¹˜R⁵, Z, X⁶, and m are defined as above; and X^(p) and X^(q)denote any of X¹˜X⁴ (which are defined as above).]

-   [2] A process for producing an organotitanium compound which    comprises reacting an acetylene compound represented by the    formula (8) below in the presence of a titanium compound represented    by the formula (2) below and a Grignard reagent represented by the    formula (3) below with a compound represented by the formula (5)    below, thereby giving the titanium compound represented by the    formula (9) and/or (10) below.

[where R¹ denotes a C₁₋₂₀ alkyl group {which may be substituted with aC₁₋₆ alkoxy group (which may be substituted with a phenyl group) orOSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆alkyl group or phenyl group)}, C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkyaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denote mutuallyindependently a halogen atom, C₁₋₆ alkyl group, or phenyl group); R⁴denotes a hydrogen atom, C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² are defined as above);and Y denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷ {where Z¹, Z³, Z⁴, Z⁵, and Z⁷denote mutually independently C═O or CR¹⁴R¹⁵ <where R¹⁴ and R¹⁵ denotemutually independently a hydrogen atom or C₁₋₆ alkyl group (which may besubstituted with a C₁₋₆ alkoxy group (which may be substituted with aphenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove))>, Z² and Z⁶ denote mutually independently O, S, C═O, NR¹⁶ <whereR¹⁶ denotes a C₁₋₆ alkyl group (which may be substituted with a C₁₋₆alkoxy group (which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above))>, or CR^(14′) R^(15′)<where R¹⁴′ and R^(15′) denote mutually independently a hydrogen atom orC₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))>}.]TiX¹X²X³X⁴  (2)[where X¹, X², X³, and X⁴ denote mutually independently a halogen atom,C₁₋₆ alkoxy group {which may be substituted with a phenyl group (whichmay be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), or a naphthyl group)}, phenoxy group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenyl group), ornaphthoxy group.]RMgX⁵  (3)[where R denotes a C₂₋₈ alkyl group having a hydrogen atom at the βposition, and X⁵ denotes a halogen atom.]

[where R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group), or naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ {where R⁶ denotes a C₁₋₆ alkyl groupor phenyl group (which may be substituted with a halogen atom or C₁₋₆alkyl group) and n denotes 1 or 2}, OSO₂R⁶ (where R⁶ is defined asabove), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkyl group);and m denotes 0 or 1.]

[where R¹, R⁴, R⁵, Y, Z, X⁶, and m are defined as above; and X^(p) andX^(q) denote any of X¹˜X⁴ (which are defined as above).]

-   [3] A process for producing an organotitanium compound which    comprises reacting an acetylene compound represented by the    formula (1) below in the presence of a titanium compound represented    by the formula (2) below and a Grignard reagent represented by the    formula (3) below with a compound represented by the formula (11)    below, thereby giving the titanium compound represented by the    formula (12) below.

[where R¹ and R² denote mutually independently a C₁₋₂₀ alkyl group{which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkyaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹R¹² (where R¹⁰,R¹¹, and R¹² denote mutually independently a halogen atom, C₁₋₆ alkylgroup, or phenyl group).]TiX¹X²X³X⁴  (2)[where X¹, X², X³, and X⁴ denote mutually independently a halogen atom,C₁₋₆ alkoxy group {which may be substituted with a phenyl group (whichmay be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), or a naphthyl group}, phenoxy group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenyl group), ornaphthoxy group).]RMgX⁵  (3)[where R denotes a C₂₋₈ alkyl group having a hydrogen atom at the βposition, and X⁵ denotes a halogen atom.]

[where R³ denotes a hydrogen atom, C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² are defined as above);R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group (whichmay be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Y′ denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷{where Z¹, Z³, Z⁴, Z⁵, and Z⁷ denote mutually independently C═O orCR¹⁴R¹⁵ <where R¹⁴ and R¹⁵ denote mutually independently a hydrogen atomor C₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))>, Z² and Z⁶ denote mutuallyindependently O, S, C═O, NR¹⁶ <where R¹⁶ denotes a C₁₋₆ alkyl group(which may be substituted with C₁₋₆ alkoxy group (which may besubstituted with a phenyl group)) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ aredefined as above)>, or CR^(14′) R^(15′) <where R^(14′) and R^(15′)denote mutually independently a hydrogen atom, C₁₋₆ alkyl group (whichmay be substituted with a C₁₋₆ alkoxy group (which may be substitutedwith a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove))>}; X⁶ denotes a halogen atom, C₁₋₆ alkoxy group {which may besubstituted with a phenyl group (which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenyl group), or naphthyl group},phenoxy group (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆alkoxy group, or phenyl group), naphthoxy group, SO_(n)R⁶ {where R⁶denotes a C₁₋₆ alkyl group or phenyl group (which may be substitutedwith a halogen atom or C₁₋₆ alkyl group), and n denotes 1 or 2}, OSO₂R⁶(where R⁶ is defined as above), or OP(O)(OR¹³)₂ group (where R¹³ denotesa C₁₋₆ alkyl group); and m denotes 0 or 1.]

[where R¹ to R³, R⁵, Y′, X⁶, and m are defined as above; and X^(p) andX^(q) denote any of X¹˜X⁴ (which are defined as above).]

-   [4] A process for producing an organotitanium compound which    comprises reacting an acetylene compound represented by the    formula (1) below in the presence of a titanium compound represented    by the formula (2) below and a Grignard reagent represented by the    formula (3) below with a compound represented by the formula (13)    below, thereby giving the titanium compound represented by the    formula (14) below.

[where R¹ and R² denote mutually independently a C₁₋₂₀ alkyl group{which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹denote mutually independently a C₁₋₆ alkyl group or phenyl group)},C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆alkylaminocarbonyl group, di-C₁₋₆-alkyaminocarbonyl group, phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆ alkyl groupor phenyl group), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denotemutually independently a halogen atom, C₁₋₆ alkyl group, or phenylgroup).]TiX¹X²X³X⁴  (2)[where X¹, X², X³, and X⁴ denote mutually independently a halogen atom,C₁₋₆ alkoxy group {which may be substituted with a phenyl group (whichmay be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup) or naphthyl group}, phenoxy group (which may be substituted witha C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenyl group), or naphthoxygroup.]RMgX⁵  (3)[where R denotes a C₂₋₈ alkyl group having a hydrogen atom at the βposition, and X⁵ denotes a halogen atom.]

[where R′ denotes a hydrogen atom or C₁₋₂₀ alkyl group; and X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group) or naphthyl group}, phenoxy group (which may besubstituted with C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenyl group),naphthoxy group, SO_(n)R⁶ group (where R⁶ denotes a C₁₋₆ alkyl group orphenyl group {which may be substituted with a halogen atom or C₁₋₆ alkylgroup), and n denotes 1 or 2}, OSO₂R⁶ (where R⁶ is defined as above), orOP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkyl group).]

[where R¹, R², R′, Z, and X⁶ are defined as above; and X^(p) and X^(q)denote any of X¹ to X⁴ (which are defined as above).]

-   [5] A process for producing an organotitanium compound as defined in    any of [1] to [4] above, wherein the titanium compound is    tetra-i-propoxytitanium.-   [6] A process for producing an organotitanium compound as defined in    any of [1] to [5] above, wherein the Grignard reagent is an i-propyl    Grignard reagent.-   [7] A process for addition reaction which comprises adding to the    organotitanium compound obtained by the process defined in any of    [1] to [6] above a compound having an electrophilic functional group    or an electrophilic reagent, and performing addition reaction on the    organotitanium compound.-   [8] A process for addition reaction as defined in [7] above, wherein    the electrophilic functional group is an aldehyde group, ketone    group, imino group, hydrazone group, aliphatic double bond,    aliphatic triple bond, acyl group, ester group, or carbonate group.-   [9] A process for addition reaction as defined in [7] above, wherein    the electrophilic reagent is water, heavy water, chlorine, bromine,    iodine, N-bromosuccinimide, oxygen, carbon dioxide gas, or carbon    monoxide.

DETAILED DESCRIPTION OF THE INVENTION

The invention will be described in more detail in the following.Incidentally, throughout this specification, “n” implies “normal”, “i”implies “iso”, “s” implies “secondary”, “t” implies “tertiary”, “c”implies “cyclo”, “o” implies “ortho”, “m” implies “meta”, and “p”implies “para”.

(A) Process For Producing Organotitanium Compound

In the acetylene compound represented by the formula (1), R¹ and R²denote mutually independently a C₁₋₂₀ alkyl group {which may besubstituted with a C₁₋₆ alkoxy group (which may be substituted with aphenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ denote mutuallyindependently a C₁₋₆ alkyl group or phenyl group)}, C₃₋₂₀ alkenyl group,C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonylgroup, di-C₁₋₆-alkyaminocarbonyl group, phenyl group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆ alkyl groupor phenyl group), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denotemutually independently a halogen atom, C₁₋₆ alkyl group, or phenylgroup).

The C₁₋₂₀ alkyl group may be a straight, branched, or cyclic one. Itincludes, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl,i-butyl, s-butyl, t-butyl, n-pentyl, c-pentyl, n-hexyl, c-hexyl,n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl,n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl,n-nonadecyl, and eicosanyl. It also includes those substituted alkylgroups, such as 2-methoxyethyl, 2-ethoxyethyl, 2-benzyloxyethyl,2-trimethylsiloxyethyl, 2-t-butyldimethylsiloxyethyl,2-t-butyldiphenylsiloxyethyl, 3-methoxypropyl, 3-ethoxypropyl,3-benzyloxypropyl, 3-trimethylsiloxypropyl,3-t-butyldimethylsiloxypropyl, 3-t-butyldiephenylsiloxypropyl,4-methoxybutyl, 4-ethoxybutyl, 4-benzyloxybutyl, 4-trimethylsiloxybutyl,4-t-butyldimethylsiloxybutyl, and 4-t-butyldiphenylsiloxybutyl.

Of these examples, favorable ones are methyl, ethyl, n-propyl, n-butyl,n-pentyl, n-hexyl, 2-methoxyethyl, 2-ethoxyethyl, 2-benzyloxyethyl,2-trimethylsiloxyethyl, 2-t-butylmethylsiloxyethyl, and2-t-butyldiphenylsiloxyethyl. Particularly favorable ones are methyl,n-butyl, n-hexyl, 2-bentyloxyethyl, and 2-t-butyldimethylsiloxyethyl.

The C₃₋₂₀ alkenyl group may be a straight, branched, or cyclic one. Itincludes, for example, allyl, 2-butenyl, 3-butenyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,6-heptenyl, 7-octenyl, 3,7-dimethyl-6-octenyl, 8-nonenyl, 9-decenyl,10-undecenyl, 11-dodecenyl, 12-tridecenyl, 13-tetradecenyl,14-pentadecenyl, 15-hexadecenyl, 16-heptadecenyl, 17-octadecenyl,18-nonadecenyl, and 19-eicosenyl. Of these examples,3,7-dimethyl-6-octenyl is favorable.

The C₁₋₆ alkoxy group may be a straight, branched, or cyclic one. Itincludes, for example, methoxy, ethoxy, n-propoxy, i-propoxy, c-propoxy,n-butoxy, i-butoxy, s-butoxy, t-butoxy, c-butoxy, 1-methyl-c-propoxy,2-methyl-c-propoxy, pentoxy, c-pentoxy, hexoxy, and c-hexoxy. Of theseexamples, favorable ones are methoxy, ethoxy, n-butoxy, c-pentoxy,n-hexoxy, and c-hexoxy. c-Hexoxy is particularly favorable.

The C₁₋₆ alkoxycarbonyl group is not specifically restricted so long asit is a carbonyl group having the above-mentioned C₁₋₆ alkoxy group. Itincludes, for example, methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl,i-butoxycarbonyl, t-butoxycarbonyl, t-amyloxycarbonyl, vinyloxycarbonyl,allyloxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl,2,2,2-trichloroethoxycarbonyl, pentoxycarbonyl, and hexoxycarbonyl. Ofthese examples, favorable ones are methoxycarbonyl, ethoxycarbonyl,n-butoxycarbonyl, and t-butoxycarbonyl, and particularly favorable onesare ethoxycarbonyl and t-butoxycarbonyl.

The C₁₋₆ alkyl group may be a straight, branched, or cyclic one. Itincludes, for example, methyl, ethyl, n-propyl, i-propyl, c-propyl,n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl,2-methyl-c-propyl, n-pentyl, 1-methyl-n-butyl, 2-methyl-n-butyl,3-methyl-n-butyl, 1,1-dimethyl-n-propyl, 1,2-dimethyl-n-propyl,2,2-dimethyl-n-propyl, 1-ethyl-n-propyl, c-pentyl, 1-methyl-c-butyl,2-methyl-c-butyl, 3-methyl-c-butyl, 1,2-dimethyl-c-propyl,2,3-dimethyl-c-propyl, 1-ethyl-c-propyl, 2-ethyl-c-propyl, n-hexyl,1-methyl-n-pentyl, 2-methyl-n-pentyl, 3-methyl-n-pentyl,4-methyl-n-pentyl, 1,1-dimethyl-n-butyl, 1,2-dimethyl-n-butyl,1,3-dimethyl-n-butyl, 2,2-dimethyl-n-butyl, 2,3-dimethyl-n-butyl,3,3-dimethyl-n-butyl, 1-ethyl-n-butyl, 2-ethyl-n-butyl,1,1,2-trimethyl-n-propyl, 1,2,2-trimethyl-n-propyl,1-ethyl-1-methyl-n-propyl, 1-ethyl-2-methyl-n-propyl, c-hexyl,1-methyl-c-pentyl, 2-methyl-c-pentyl, 3-methyl-c-pentyl,1-ethyl-c-butyl, 2-ethyl-c-butyl, 3-ethyl-c-butyl, 1,2-dimethyl-c-butyl,1,3-dimethy c-butyl, 2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl,2,4-dimethyl-c-butyl, 3,3-dimethyl-c-butyl, 1-n-propyl-c-propyl,2-n-propyl-c-propyl, 1-i-propyl-c-propyl, 2-i-propyl-c-propyl,1,2,2-trimethyl-c-propyl, 1,2,3-trimethyl-c-propyl,2,2,3-trimethyl-c-propyl, 1-ethyl-2-methyl-c-propyl,2-ethyl-1-methyl-c-propyl, 2-ethyl-2-methyl-c-propyl, and2-ethyl-3-methyl-c-propyl.

The C₁₋₆ alkylaminocarbonyl group and di-C₁₋₆-alkylaminocarbonyl groupare not specifically restricted so long as they are(di)alkylaminocarbonyl groups having the above-mentioned C₁₋₆ alkylgroup on the nitrogen atom. They include, for example,(di)methylaminocarbonyl, (di)ethylaminocarbonyl,(di)propylaminocarbonyl, and (di)butylaminocarbonyl. Of these examples,favorable ones are (di)methylaminocarbonyl, (di)ethylaminocarbonyl, and(di)n-propylaminocarbonyl. Particularly favorable one is(di)ethylaminocarbonyl.

The phenyl group includes, for example, phenyl, o-methylphenyl,m-methylphenyl, p-methylphenyl, p-ethylphenyl, p-i-propylphenyl,p-t-butylphenyl, o-methoxyphenyl, p-methoxyphenyl, 3,5-dimethylphenyl,3,5-dimethoxyphenyl, 3,5-diethylphenyl, 3,5-di-i-propylphenyl,2,4,6-trimethylphenyl, and 2,4,6-trimethoxyphenyl. Of these examples,phenyl is favorable.

The SiR⁷R⁸R⁹ group is not specifically restricted so long as itssubstituent groups (any of R⁷, R⁸, and R⁹) are mutually independently aC₁₋₆ alkyl group or phenyl group. It includes, for example,trimethylsilyl, triethylsilyl, triisopropylsilyl, tributylsilyl,t-butyldimethylsilyl, t-butyldiphenylsilyl, diphenylmethylsilyl, andtriphenylsilyl. Of these examples, favorable ones are trimethylsilyl,t-butyldimethylsilyl, and t-butyldiphenylsilyl. Particularly favorableones are trimethylsilyl and t-butyldimethylsilyl.

The SnR¹⁰R¹¹R¹² group is not specifically restricted so long as itssubstituent groups (any of R¹⁰, R¹¹, and R¹²) are mutually independentlya halogen atom, C₁₋₆ alkyl group, or phenyl group. It includes, forexample, trimethyltin, triethyltin, tributyltin, trichlorotin, andtriphenyltin. Of these examples, favorable ones are trimethyltin,triphenyltin, and trichlorotin.

Incidentally, the halogen atom may be any of fluorine, chlorine,bromine, and iodine.

In the titanium compound represented by the formula (2) above, X¹, X²,X³, and X⁴ denote mutually independently a halogen atom, C₁₋₆ alkoxygroup {which may be substituted with a phenyl group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenyl group)or naphthyl group}, phenoxy group (which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenoxy group), or naphthoxy group.

The C₁₋₆ alkoxy group includes (in addition to the above-exemplifiedalkoxy groups) benzyloxy, o-methylbenzyloxy, m-methylbenzyloxy,p-methylbenzyloxy, o-methoxybenzyloxy, p-methoxybenzyloxy, phenethyloxy,o-methylphenethyloxy, m-methylphenethyloxy, p-methylphenethyloxy,o-methoxyphenethyloxy, p-methoxyphenethyloxy, 3-pheylpropoxy,4-phenylbutoxy, 5-phenylpentoxy, 6-phenylhexoxy, a-naphthylmethoxy,β-naphthylmethoxy, o-biphenylylmethoxy, m-biphenylylmethoxy,p-biphenylylmethoxy, α-naphthylethoxy, β-naphthylethoxy,o-biphenylylethoxy, m-biphenylylethoxy, and p-biphenylylethoxy. Of theseexamples, favorable ones are methoxy, ethoxy, n-propoxy, i-propoxy, andn-butoxy.

The phenoxy group or naphthoxy group is not specifically restricted; itincludes, for example, phenoxy, o-methylphenoxy, m-methylphenoxy,p-methylphenoxy, p-ethylphenoxy, p-i-propylphenoxy, p-t-butylphenoxy,o-methoxyphenoxy, p-methoxyphenoxy, α-naphthoxy, β-naphthoxy,o-biphenyloxy, m-biphenyloxy, and p-biphenyloxy.

The halogen atom X is not specifically restricted as mentioned above. Afavorable halogen is chlorine.

Incidentally, the C₁₋₆ alkyl group is defined as above.

Typical examples of the titanium compound includetetra-i-propoxytitanium, chlorotri-i-propoxytitanium, anddichlorodi-i-propoxytitanium. Of these examples, tetra-i-propoxytitaniumis favorable.

In the Grignard reagent represented by the formula (3) above, R denotesa C₂₋₈ alkyl group having a hydrogen atom at the β position, and X⁵denotes a halogen atom.

R (which is a C₂₋₈ alkyl group having a hydrogen atom at the β position)may be a straight, branched, or cyclic alkyl group which is notspecifically restricted so long as it has a hydrogen atom at the βposition. It includes, for example, ethyl, n-propyl, i-propyl, c-propyl,n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl,2-methyl-c-propyl, n-pentyl, 1-methyl-n-butyl, 2-methyl-n-butyl,3-methyl-n-butyl, 1,1-dimethyl-n-propyl, 1,2-dimethyl-n-propyl,1-ethyl-n-propyl, c-pentyl, 1-methyl-c-butyl, 2-methyl-c-butyl,3-methyl-c-butyl, 1,2-dimethyl-c-propyl, 2,3-dimethyl-c-propyl,1-ethyl-c-propyl, 2-ethyl-c-propyl, n-hexyl, 1-methyl-n-pentyl,2-methyl-n-pentyl, 3-methyl-n-pentyl, 4-methyl-n-pentyl,1,1-dimethyl-n-butyl, 1,2-dimethyl-n-butyl, 1,3-dimethyl-n-butyl,2,3-dimethyl-n-butyl, 3,3-diemthyl-n-butyl, 1-ethyl-n-butyl,2-ethyl-n-butyl, 1,1,2-trimethyl-n-propyl, 1-ethyl-1-methyl-n-propyl,1-ethyl-2-methyl-n-propyl, c-hexyl, 1-methyl-c-pentyl,2-methyl-c-pentyl, 3-methyl-c-pentyl, 1-ethyl-c-butyl, 2-ethyl-c-butyl,3-ethyl-c-butyl, 1,2-dimethyl-c-butyl, 1,3-dimethyl-c-butyl,2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl, 2,4-dimethyl-c-butyl,3,3-dimethyl-c-butyl, 1-n-propyl-c-propyl, 2-n-propyl-c-propyl,1-i-propyl-c-propyl, 2-i-propyl-c-propyl, 1,2,2-trimethyl-c-propyl,1,2,3-trimethyl-c-propyl, 2,2,3-trimethyl-c-propyl,1-ethyl-2-methyl-c-propyl, 2-ethyl-1-methyl-c-propyl,2-ethyl-2-methyl-c-propyl, 2-ethyl-3-methyl-c-propyl, n-heptyl,5-methyl-n-hexyl, c-heptyl, n-octyl, 6-methyl-n-heptyl, and c-octyl. Ofthese examples, favorable ones are ethyl, n-propyl, i-propyl, n-butyl,and i-butyl.

The halogen atom (X⁵) is not specifically restricted. Favorable ones arechlorine and bromine.

Typical examples of the Grignard reagent include ethyl Grignard reagent(such as ethyl magnesium chloride and ethyl magnesium bromide), n-propylGrignard reagent (such as n-propyl magnesium chloride and n-propylmagnesium bromide), and i-propyl Grignard reagent (such as i-propylmagnesium chloride and i-propyl magnesium bromide). Of these examples, afavorable one is i-propyl Grignard reagent.

In the acetylene compound represented by the formula (4) above, R³ andR⁴ denote mutually independently a hydrogen atom, C₁₋₂₀ alkyl group,C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonylgroup, di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹R¹² (where R¹⁰,R¹¹, and R¹² are defined as above).

The C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, di-C₁₋₆-alkylaminocarbonyl group,SiR⁷R⁸R⁹ group, and SnR¹⁰R¹¹R¹² group are the same as those defined inthe acetylene compound represented by the formula (1) above.

In the compound represented by the formula (5) above, R⁵ denotes ahydrogen atom, C₁₋₂₀ alkyl group, or phenyl group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group) or naphthyl group}, phenoxy group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ group {where R⁶ denotes a C₁₋₆ alkylgroup or phenyl group (which may be substituted with a halogen atom orC₁₋₆ alkyl group) and n denotes 1 or 2}, OSO₂R⁶ group (where R⁶ isdefined as above), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkylgroup); and m denotes 0 or 1.

The SO_(n)R⁶ group is not specifically restricted; it includes, forexample, methanesulfinyl, p-toluenesulfinyl, p-trifluoromethanesulfinyl,methanesulfonyl, benzenesuflonyl, p-toluenesulfonyl, andp-trifluoromethanesulfonyl. Of these examples, favorable ones arep-toluenesulfonyl and p-toluenesulfinyl.

The OSO₂R⁶ group is not specifically restricted; it includes, forexample, methanesulfonyloxy, benzenesufonyloxy, p-toluenesulfonyloxy,and p-trifluoromethanesulfonyloxy groups. Of these examples, a favorableone is p-toluenesulfonyloxy group.

The OP(O)(OR¹³)₂ group is not specifically restricted; it includes, forexample, dimethyl phosphate, diethyl phosphate, and diphenyl phosphate.Of these example, a favorable one is diethyl phosphate.

Incidentally, the C₁₋₂₀ alkyl group, phenyl group, C₁₋₆ alkoxycarbonylgroup, C₁₋₆ alkylaminocarbonyl group, di-C₁₋₆-alkylaminocarbonyl group,halogen atom, C₁₋₆ alkoxy group, phenoxy group, and naphthoxy group arethe same as those defined above.

In the diyne compound in the formula (8) above, the terminal substituentgroups R¹ and R⁴ are also defined as above.

Y denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷ {where Z¹, Z³, Z⁴, Z⁵, and Z⁷ denotemutually independently C═O or CR¹⁴R¹⁵ <where R¹⁴ and R¹⁵ denote mutuallyindependently a hydrogen atom or C₁₋₆ alkyl group (which may besubstituted with a C₁₋₆ alkoxy group (which may be substituted with aphenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove))>, Z² and Z⁶ denote mutually independently O, S, C═O, NR¹⁶ <whereR¹⁶ denotes a C₁₋₆ alkyl group (which may be substituted with a C₁₋₆alkoxy group (which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above))>, or CR^(14′) R^(15′)<where R^(14′) and R^(15′) denote mutually independently a hydrogenatom, C₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxygroup (which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (whereR⁷, R⁸, and R⁹ are defined as above))>}.

Y is not specifically restricted; it includes, for example, (CH₂)₃,(CH₂)₄, CH₂C(CH₂OCH₂Ph)₂CH₂, CH₂C(CH₂OSiMe₃)₂CH₂,CH₂C(CH₂OSit-BuMe₂)₂CH₂, CH₂C(CH₂OCH₃)₂CH₂, CH₂OCH₂, CH₂SCH₂,CH₂C(O)CH₂, C(O)N(CH₂Ph)CH₂, C(O)N(CH₃)CH₂, C(O)N(CH₂Ph)C(O), andC(O)N(CH₃)C(O). Of these examples, favorable ones are (CH₂)₃,CH₂C(CH₂OCH₂Ph)₂CH₂, and C(O)N(CH₂Ph)CH₂. Me stands for a methyl group,Ph stands for a phenyl group, and t-Bu stands for a t-butyl group.

In the compound represented by the formula (11) or (13), R³, R⁵, R′, andX⁶ are defined as above. Y′ is the same as Y mentioned above.

A mention is given below of the process for producing the organotitaniumcompound represented by the formula (6) and/or (7).

The process consists of reacting an acetylene compound represented bythe formula (1) in the presence of a titanium compound represented bythe formula (2) and a Grignard reagent represented by the formula (3)with a compound represented by the formula (4) and further reacting witha compound represented by the formula (5), thereby giving the titaniumcompound represented by the formula (6) and/or (7) above.

The molar amount of the titanium compound used in this reaction shouldbe 0.01–5 times, preferably 0.5–2 times, the amount of the acetylenecompound (as the substrate) represented by the formula (1). The molaramount of the Grignard reagent should be 1–10 times the amount of thetitanium compound used. The amount should be limited to 1.5–2.5 times inorder to avoid side reactions with the substrate.

The reaction may be carried out by adding the reactants in any order.One procedure involves mixing the titanium compound and the Grignardreagent and then adding to the mixture the acetylene compound (as thesubstrate) represented by the formula (1). Another procedure involvesadding the titanium compound to the acetylene compound represented bythe formula (1), and then adding the Grignard reagent. Either procedurewill do.

The molar amount of the compound represented by the formula (4) shouldbe 0.5–2 times, preferably 0.6–1.2 times, the amount of the acetylenecompound represented by the formula (1).

The molar amount of the compound represented by the formula (5) shouldbe 0.5–2 times, preferably 0.8–1.5 times, the amount of the acetylenecompound represented by the formula (1).

The solvent used in the reaction is not specifically restricted so longas it is not involved in the reaction. It includes, for example,aromatic hydrocarbons (such as benzene, toluene, xylene, mesitylene,chlorobenzene, and o-dichlorobenzene), aliphatic hydrocarbons (such asn-hexane, cyclohexane, n-octane, and n-decane), halogenated hydrocarbons(such as dichloromethane, dichloroethane, chloroform, and carbontetrachloride), and ethers (such as tetrahydrofuran, diethyl ether,t-butyl methyl ether, and dimethoxyethane). Of these examples, favorableones are dichloromethane, tetrahydrofuran, and diethyl ether. They maybe used alone or in combination with one another.

The reaction temperature is not specifically restricted; it may rangefrom −100° C. to the boiling point of the solvent. Preferred reactiontemperatures are within the range from −80° C. to 40° C. The reactiontime is usually 0.1 to 1000 hours.

The above-mentioned reaction gives rise to the organotitanium compoundrepresented by the above-mentioned formula (6) and/or (7). This compoundis unstable out of the reaction system. Therefore, it is not isolated assuch. Instead, the reaction system is given an electrophilic reagent tobring about addition reaction at the titanium bonding position, and theresulting addition product is isolated afterwards.

After the reaction is complete, the reaction system is given an aqueoussolution of alkali to produce an aromatic compound in which a hydrogenatom is added to the titanium bonding position. Subsequently, thisaromatic compound is extracted with an adequate solvent, and there isobtained a crude product upon condensation under reduced pressure. Ifnecessary, the crude product is purified in the usual way bydistillation, recrystallization, silica gel column chromatography, orthe like. In this way it is possible to isolate the addition product inpure form.

It is presumed that the organotitanium compound represented by theformula (6) or (7) is formed by the following reaction mechanism.

The titanium compound and the Grignard reagent give rise to a divalenttitanium complex, which reacts with the first acetylene compoundrepresented by the formula (1) to give a titanacyclopropeneintermediate. This intermediate reacts with the second acetylenecompound represented by the formula (4) to give a titanacyclopendadieneintermediate. Between this intermediate and the compound represented bythe formula (5) occurs cyclic addition reaction. This addition reactioneliminates the leaving group, thereby giving rise to the organotitaniumcompound represented by the formula (6) or (7).

It is presumed that the ratio in which the above-mentionedorganotitanium compound is formed (or the orientation of the cyclicaddition reaction) varies depending mainly on the electron-attractingproperty of the substituent group at the 1- and 4-position of thecyclopentadiene intermediate.

A mention is made below of the process for producing the organotitaniumcompound represented by the formulas (9) and/or (10) above.

The diyne compound represented by the formula (8) is reacted with thecompound represented by the formula (4) above in the presence of thetitanium compound represented by the formula (2) above and the Grignardreagent represented by the formula (3) above. The resulting reactionproduct is further reacted with the compound represented by the formula(5) to give the organotitanium compound represented by the formulas (9)and/or (10) above.

The molar amount of the titanium compound used in this reaction is0.01–5 times, preferably 0.5–2 times, the amount of the diyne compound(as the substrate) represented by the formula (8). The molar amount ofthe Grignard reagent should be 1–10 times the amount of the titaniumcompound used. The amount should be limited to 1.5–2.5 times in order toavoid side reactions with the substrate.

The reaction may be carried out by adding the reactants in any order.One procedure involves mixing the titanium compound and the Grignardreagent and then adding to the mixture the diyne compound (as thesubstrate) represented by the formula (8). Another procedure involvesadding the titanium compound to the diyne compound represented by theformula (8), and then adding the Grignard reagent. Either procedure willdo.

The molar amount of the compound represented by the formula (5) shouldbe 0.5–2 times, preferably 0.8–1.5 times, the amount of the diynecompound represented by the formula (8).

The solvent used in the reaction is not specifically restricted so longas it is not involved in the reaction. It includes those which have beenlisted above.

The reaction temperature is not specifically restricted; it may rangefrom −100° C. to the boiling point of the solvent. Preferred reactiontemperatures are within the range from −80° C. to 40° C. The reactiontime is usually 0.1 to 1000 hours.

The above-mentioned reaction gives rise to the organotitanium compoundrepresented by the above-mentioned formula (9) and/or (10). Thiscompound is unstable out of the reaction system. Therefore, it is notisolated as such. Instead, the reaction system is given an electrophilicreagent to bring about addition reaction at the titanium bondingposition, and the resulting addition product is isolated afterwards.

It is presumed that the organotitanium compound represented by theformula (9) or (10) is formed by the following reaction mechanism. Thereaction mechanism is identical with that mentioned above, except thattwo molecules of the acetylene compounds represented by the formulas (1)and (4) are replaced by the diyne compound represented by the formula(8).

A mention is made below of the process for producing the organotitaniumcompound represented by the formulas (12) above.

The diyne compound represented by the formula (11) is reacted with theacetylene compound represented by the formula (1) above in the presenceof the titanium compound represented by the formula (2) above and theGrignard reagent represented by the formula (3) above. In this way it ispossible to produce the organotitanium compound represented by theformula (12) above.

The molar amount of the titanium compound used in this reaction is0.01–5 times, preferably 0.5–2 times, the amount of the acetylenecompound (as the substrate) represented by the formula (1). The molaramount of the Grignard reagent should be 1–10 times the amount of thetitanium compound used. The amount should be limited to 1.5–2.5 times inorder to avoid side reactions with the substrate.

The reaction may be carried out by adding the reactants in any order.One procedure involves mixing the titanium compound and the Grignardreagent and then adding to the mixture the acetylene compound (as thesubstrate) represented by the formula (1). Another procedure involvesadding the titanium compound to the acetylene compound represented bythe formula (1), and then adding the Grignard reagent. Either procedurewill do.

The molar amount of the diyne compound represented by the formula (11)is 0.5–2 times, preferably 0.8–1.5 times, the amount of the acetylenecompound represented by the formula (1).

The solvent used in the reaction is not specifically restricted so longas it is not involved in the reaction. It includes those which have beenlisted above.

The reaction temperature is not specifically restricted; it may rangefrom −100° C. to the boiling point of the solvent. Preferred reactiontemperatures are within the range from −80° C. to 40° C. The reactiontime is usually 0.1 to 1000 hours.

The above-mentioned reaction gives rise to the organotitanium compoundrepresented by the above-mentioned formula (12). This compound isunstable out of the reaction system. Therefore, it is not isolated assuch. Instead, the reaction system is given an electrophilic reagent tobring about addition reaction at the titanium bonding position, and theresulting addition product is isolated afterwards.

It is presumed that the organotitanium compound represented by theformula (12) is formed by the following reaction mechanism. The reactionmechanism is identical with that mentioned above, except that twomolecules of the acetylene compounds represented by the formulas (4) and(5) are replaced by the diyne compound represented by the formula (11).The reaction product has such a structure that the titanacyclopentadieneintermediate is connected to the acetylene compound as the thirdcomponent. This determines the orientation of the cyclic addition andgives rise to a single organotitanium compound.

A mention is made below of the process for producing the organotitaniumcompound represented by the formulas (14) above.

The acetylene compound represented by the formula (1) is reacted withtwo molecules of the acetylene compound represented by the formula (13)above in the presence of the titanium compound represented by theformula (2) above and the Grignard reagent represented by the formula(3) above. In this way it is possible to produce the organotitaniumcompound represented by the formula (14) above.

The molar amount of the titanium compound used in this reaction is0.01–5 times, preferably 0.5–2 times, the amount of the acetylenecompound (as the substrate) represented by the formula (1). The molaramount of the Grignard reagent should be 1–10 times the amount of thetitanium compound used. The amount should be limited to 1.5–2.5 times inorder to avoid side reactions with the substrate.

The reaction may be carried out by adding the reactants in any order.One procedure involves mixing the titanium compound and the Grignardreagent and then adding to the mixture the acetylene compound (as thesubstrate) represented by the formula (1). Another procedure involvesadding the titanium compound to the acetylene compound represented bythe formula (1), and then adding the Grignard reagent. Either procedurewill do.

The molar amount of the acetylene compound represented by the formula(13) is 1–4 times, preferably 1.6–3 times, the amount of the acetylenecompound represented by the formula (1).

The solvent used in the reaction is not specifically restricted so longas it is not involved in the reaction. It includes those which have beenlisted above.

The reaction temperature is not specifically restricted; it may rangefrom −100° C. to the boiling point of the solvent. Preferred reactiontemperatures are within the range from −80° C. to 40° C. The reactiontime is usually 0.1 to 1000 hours.

The above-mentioned reaction gives rise to the organotitanium compoundrepresented by the above-mentioned formula (14). This compound isunstable out of the reaction system. Therefore, it is not isolated assuch. Instead, the reaction system is given an electrophilic reagent tobring about addition reaction at the titanium bonding position, and theresulting addition product is isolated afterwards.

It is presumed that the organotitanium compound represented by theformula (14) is formed by the following reaction mechanism.

The titanium compound and the Grignard reagent give rise to a divalenttitanium complex, which reacts with two molecules of the compoundshaving a triple bond to give a titanacyclopentadiene intermediate. Thisintermediate reacts with one molecule of the compound represented by theformula (13) for cyclic addition reaction. This addition reaction bringsabout transfer of titanium-carbon bond and eliminates the leaving group,thereby giving rise to the organotitanium compound represented by theformula (14).

(B) Process For Addition Reaction

According to the present invention, the process for addition reactionconsists of adding to the organotitanium compound obtained by theabove-mentioned process a compound having an electrophilic functionalgroup or an electrophilic reagent, and performing addition reaction onthe organotitanium compound.

The electrophilic functional group is not specifically restricted solong as it reacts with the organotitanium compound of the presentinvention. It is preferably aldehyde group, ketone group, imino group,hydrazone group, aliphatic double bond, aliphatic triple bond, acylgroup, ester group, or carbonate group. The compound having anelectrophilic functional group includes, for example, aldehyde compound,ketone compound, imine compound, hydrazone compound, olefin compound,acetylene compound, acyl compound, ester compound, α,β-unsaturatedcarbonyl compound, and carbonate ester compound.

The aldehyde compound is not specifically restricted. It includes, forexample, C₁₋₁₀ alkyl aldehyde, C₄₋₆ cycloalkyl aldehyde, C₃₋₁₄cycloalkenyl aldehyde, benzaldehyde, o-halogenobenzaldehyde,m-halogenobenzaldehyde, p-halogenobenzaldehyde, C₁₋₁₀ alkylester-substituted phenyl aldehyde, o-halogenosuccin aldehyde,m-halogenosuccin aldehyde, p-halogenosuccin aldehyde, furylaldehyde, andthiophen aldehyde.

The ketone compound includes, for example, C₃₋₂₀ alkyl ketone, C₄₋₃₀alkyl ester-substituted alkyl ketone, C₃₋₁₀ cycloalkyl ketone,acetophenone, tetralone, decalone, furyl ketone, and thiophenoketone.The imine compound includes, for example, the reaction product of theabove-mentioned aldehyde compound with C₁₋₁₀ alkylamine, aniline, orbenzylamine.

The hydrazone compound includes, for example, the reaction product ofthe above-mentioned ketone compound with C₁₋₁₀ alkyl hydrazine.

The olefin compound includes, for example, allyl alcohol derivativeswhich may have a substituent group. The allyl alcohol derivativeincludes, for example, C₄₋₁₃ allyl alcohol alkyl ester and C₄₋₁₃ allylalcohol alkyl carbamate.

The allyl alcohol derivative may have a substituent group such as C₁₋₂₀alkyl group, phenyl group, o-halogenophenyl group, m-halogenophenylgroup, and p-halogenophenyl group.

The acetylene compound includes, for example, propargyl alcoholderivative which may have a substituent group and propargyl halide whichmay have a substituent group. The propargyl alcohol derivative includes,for example, C₄₋₁₃ propargyl alcohol alkyl ester, C₄₋₁₃ propargylalcohol alkyl carbamate, C₄₋₁₃ propargyl alcohol alkyl ether, C₄₋₁₃propargyl alcohol alkylsulfonic ester, propargylalcohol-o-hydroxyphenylsulfonic ester, propargylalcohol-m-hydroxyphenylsulfonic ester, propargylalcohol-p-hydroxyphenylsulfonic ester, and C₄₋₁₃ propargyl alcohol alkylphosphoric ester.

The propargyl halide includes, for example, propargyl chloride andpropargyl bromide.

These propargyl alcohol derivatives and propargyl halides may have asubstituent group such as C₁₋₂₀ alkyl group, phenyl group,o-halogenophenyl group, m-halogenophenyl group, p-halogenophenyl group,and trialkylsilyl group.

The electrophilic reagent is not specifically restricted so long as itreacts with the organotitanium compound of the present invention. It ispreferably water, heavy water, chlorine, bromine, iodine,N-bromosuccinimide, oxygen, carbon dioxide gas, or carbon monoxide.

To be concrete, the process consists of adding to the organotitaniumcompound (prepared as mentioned above) the compound having anelectrophilic functional group or the electrophilic reagent (which arecollectively referred to as an electrophilic compound hereinafter),thereby causing addition reaction with the electrophilic compound totake place at the titanium bonding position.

The molar amount of the electrophilic compound should be 1–10 times,preferably 1–5 times, particularly 1–2 times, the amount of theorganotitanium compound.

The reaction may be carried out by adding the electrophilic compound inany order. One procedure involves adding the electrophilic compounddirectly to the reaction system in which the organotitanium compound hasbeen prepared. Another procedure involves adding a solution of theorganotitanium compound to a solution in which the electrophiliccompound has been dissolved. Either procedure will do.

The solvent used in the reaction is not specifically restricted so longas it is not involved in the reaction. It includes those which have beenused for the production of the organotitanium compound.

The reaction temperature is not specifically restricted; it may rangefrom −100° C. to the boiling point of the solvent. Preferred reactiontemperatures are within the range from −80° C. to 40° C. The reactiontime is usually 0.1 to 1000 hours.

After the reaction is complete, the addition reaction product isextracted with an adequate solvent, and there is obtained a crudeproduct upon condensation under reduced pressure. If necessary, thecrude product is purified in the usual way by distillation,recrystallization, silica gel column chromatography, or the like. Inthis way it is possible to isolate the desired product in pure form.

EXAMPLES

The invention will be described in more detail with reference to thefollowing examples, which are not intended to restrict the scopethereof.

In the structural formulas given below, Me denotes methyl group, Etdenotes ethyl group, Bn denotes benzyl group, t-Bu denotes t-butylgroup, Ph denotes phenyl group, Tol denotes p-tolyl group, and TBSdenotes t-butyldimethylsilyl group.

Example 1 3-(t-butoxycarbonyl)-4-hexylphenyl p-tolylsulfone

To a diethyl ether solution (7 mL) containing t-butyl 2-nonynoate (100mg, 0.475 mmol) and tetra-i-propoxytitanium (0.175 mL, 0.594 mmol) wasadded i-propylmagnesium chloride (1.48 M diethyl ether solution, 0.900mL, 1.33 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution kept at −50° C. was given adiethyl ether solution (2 mL) containing powderyp-toluenesulfonylacetylene (171 mg, 0.951 mmol). Stirring was continuedfor 1 hour.

The reaction solution at room temperature was stirred for 3 hours andthen given hydrochloric acid (1 mol/L) to suspend the reaction. Thereaction product was extracted with diethyl ether.

The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product was analyzed indetail by ¹H NMR. It was found to contain no other isomers. The crudeproduct was purified by silica gel column chromatography (n-hexane-ethylacetate). There was obtained 3-(t-butoxy-carbonyl)-4-hexylphenylp-tolylsulfone (98 mg, 50%) in the form of colorless oily substance.

¹H NMR: δ 0.84 (t, J=6.6 Hz, 3H, Me), 1.12–1.40 (m, 6H, alkyl H),1.45–1.65 (m, 2H, alkyl H), 1.58 (s, 9H, C(CH₃)₃), 2.37 (s, 3H, PhMe),2.90 (t, J=7.8 Hz, 2H, PhCH₂), 7.28 (d, J=8.4 Hz, 2H, Ph-H), 7.32 (d,J=8.1 Hz, 1H, Ph-H), 7.81 (d, J=8.4 Hz, 2H, Ph-H), 7.86 (dd, J=2.1, 8.1Hz, 1H, Ph-H), 8.23 (d, J=2.1 Hz, 1H, Ph-H).

The structure was confirmed (identified) by the fact that a 12% increasein NOE (nuclear Overhauser effect) due to proton at δ 2.90 ppm (PhCH₂)was observed in the peak at δ 7.32 ppm (Ph-H).

¹³C NMR: δ 13.84, 21.37, 22.35, 27.95 (C(CH₃)₃), 29.18, 31.39, 31.49,34.21, 82.30 (CO₂C), 127.74 (o- or m-Ph), 129.26 (Ph), 129.47 (Ph),129.98 (o- or m-Ph), 131.73 (Ph), 133.18 (Ph), 138.53 (Ph), 139.48 (Ph),144.30 (Ph), 149.06 (Ph), 165.05 (C═O).

IR (neat): 3070 (Ph), 2960, 2927, 2860, 1715 (C═O), 1597, 1457, 1369(S═O), 1256, 1156 (S═O), 914, 846, 813 cm⁻¹.

Elemental analysis: calculated (C₂₄H₃₂O₄S): C, 69.20%; H, 7.74%. found:C, 69.16%; H, 7.62%.

Example 2 3,4-dibutylphenyl p-tolylsulfone

To a diethyl ether solution (1.5 mL) containing 5-decyne (0.020 mL,0.111 mmol) and tetra-i-propoxytitanium (0.041 mL, 0.139 mmol) was addedi-propylmagnesium chloride (1.63 M diethyl ether solution, 0.192 mL,0.312 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 2 hours at −50° C. The solution (kept at −50° C.) wasgiven a diethyl ether solution (1 mL) containing powderyp-toluenesulfonyl-acetylene (40 mg, 0.223 mmol). Stirring was continuedfor 1 hour.

The reaction solution at room temperature was stirred for 3 hours andthen given hydrochloric acid (1 mol/L) to suspend the reaction. Thereaction product was extracted with diethyl ether.

The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product was analyzed indetail by ¹H NMR. It was found that it contained no other isomers. Thecrude product was purified by silica gel column chromatography(n-hexane-ethyl acetate). There was obtained 3,4-dibutylphenylp-tolylsulfone (25 mg, 65%) in the form of colorless oily substance.

¹H NMR: δ 0.92 (t, J=7.5 Hz, 3H, Me), 0.94 (t, J=7.5 Hz, 3H, Me), 1.38(sextet, J=7.5 Hz, 4H, alkyl H), 1.52 (quintet, J=7.5 Hz, 4H, alkyl H),2.39 (s, 3H, PhMe), 2.61 (t, J=7.5 Hz, 2H, PhMe), 2.62 (t, J=7.5 Hz, 2H,PhCH₂), 7.23 (d, J=8.1 Hz, 1H, Ph-H), 7.28 (d, J=8.4 Hz, 2H, Ph-H), 7.63(dd, J=2.1, 8.1 Hz, 1H, Ph-H), 7.70 (d, J =2.1 Hz, 1H, Ph-H), 7.82 (d,J=8.4 Hz, 2H, Ph-H).

¹³C NMR: δ 13.78 (2 peaks), 21.42, 22.58 (2 peaks), 32.21, 32.26, 32.87,32.89, 124.97 (Ph), 127.63 (o- or m-Ph), 127.96 (Ph), 129.87 (o- orm-Ph), 130.01 (Ph), 139.05 (Ph), 139.32 (Ph), 142.09 (Ph), 143.86 (Ph),146.64 (Ph).

IR (neat): 3060 (Ph), 3020 (Ph), 2957, 2929, 2870, 1597, 1465, 1402,1379, 1320 (S═O), 1301, 1179, 1154 (S═O), 1107, 1085, 911, 812, 733,708, 683 cm⁻¹.

Elemental analysis: calculated (C₂₁H₂₈O₂S): C, 73.21%; H, 8.19%. found:C, 73.04%; H, 8.07%.

Example 3 5-(t-butoxycarbonyl)-2-deuterio-4-hexylphenyl p-tolylsulfone

The same procedure as in Example 1 was repeated except that heavy waterwas added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained 5-(t-butoxycarbonyl)-2-deuterio-4-hexylphenylp-tolylsulfone.

¹H NMR: δ 0.84 (t, J=6.6 Hz, 3H, Me), 1.12–1.40 (m, 6H, alkyl H),1.45–1.65 (m, 2H, alkyl H), 1.58 (s, 9H, C(CH₃)₃), 2.37 (s, 3H, PhMe),2.90 (t, J=7.8 Hz, 2H, PhCH₂), 7.28 (d, J=8.4 Hz, 2H, Ph-H), 7.32 (s,1H, Ph-H), 7.81 (d, J=8.4 Hz, 2H, Ph-H), 8.23 (s, 1H, Ph-H).

An introduction of 78% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.86 (Ph-H) of3-(t-butoxycarbonyl)-4-hexylphenyl p-tolylsulfone.

Example 4 4,5-dibutyl-2-deuteriophenyl p-tolylsulfone

The same procedure as in Example 2 was repeated except that heavy waterwas added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained 4,5-dibutyl-2-deuteriophenyl p-tolylsulfone.

¹H NMR: δ 0.92 (t, J=7.5 Hz, 3H, Me), 0.94 (t, J=7.5 Hz, 3H, Me), 1.38(sextet, J=7.5 Hz, 4H, alkyl H), 1.52 (quintet, J=7.5 Hz, 4H, alkyl H),2.39 (s, 3H, PhMe), 2.61 (t, J=7.5 Hz, 2H, PhCH₂), 2.62 (t, J=7.5 Hz,2H, PhCH₂), 7.23 (s, 1H, Ph-H), 7.28 (d, J=8.4 Hz, 2H, Ph-H), 7.70 (s,1H, Ph-H), 7.82 (d, J=8.4 Hz, 2H, Ph-H).

An introduction of 80% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.63 (Ph-H) of3,4-dibutylphenyl p-tolylsulfone.

Example 5 t-butyl 2,4-dihexylbenzoate

To a diethyl ether solution (1.5 mL) containing t-butyl 2-nonynoate (20mg, 0.095 mmol) and tetra-i-propoxytitanium (0.035 mL, 0.119 mmol) wasadded i-propylmagnesium chloride (1.63 M diethyl ether solution, 0.163mL, 0.266 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution (kept at −50° C.) was given1-octyne (0.011 mL, 0.076 mmol), and the solution was stirred for 3hours. The solution was given a diethyl ether solution (1 mL) containingpowdery p-toluenesulfonylacetylene (21 mg, 0.114 mmol). The reactionsolution was heated to room temperature.

The reaction solution (at room temperature) was stirred for 3 hours andthen given hydrochloric acid (1 mol/L) to suspend the reaction. Thereaction product was extracted with diethyl ether. The organic layer waswashed with an aqueous solution of sodium bicarbonate and then driedwith anhydrous sodium sulfate. The solvent was distilled away underreduced pressure. There was obtained a crude product in the form of oilysubstance. The crude product was analyzed in detail by ¹H NMR. It wasfound to contain no other isomers. The crude product was purified bysilica gel column chromatography (n-hexane-diethyl ether). There wasobtained t-butyl 2,4-dihexylbenzoate (15 mg, 57%) in the form ofcolorless oily substance.

¹H NMR: δ 0.87, (t, J=7.5 Hz, 6H, Me), 1.20–1.42 (m, 16H, alkyl H), 1.58(s, 9H, C(CH₃)₃), 2.58 (t, J=7.8 Hz, 2H, PhCH₂), 2.89 (t, J=7.8 Hz, 2H,PhCH₂), 7.00 (s, 1H, Ph-H), 7.01 (d, J=8.4 Hz, 1H, Ph-H), 7.67 (d, J=8.4Hz, 1H, Ph-H).

The structure was confirmed (identified) by the fact that a 5% increasein NOE due to irradiate proton at δ 2.58 ppm (PhCH₂) was observed inboth the peak at δ 7.00 ppm (Ph-H) and the peak at δ 7.01 ppm (Ph-H) andthe fact that a 9% increase in NOE due to proton at δ 2.89 ppm (PhCH₂)was observed in the peak at δ 7.00 ppm (Ph-H).

¹³C NMR: δ 13.96 (2 peaks), 22.49, 22.53, 28.15 (C(CH₃)₃), 28.87, 29.38,31.08, 31.60, 31.74, 31.89, 34.44, 35.71, 80.76 (CO₂C), 125.73 (Ph),129.25 (Ph), 130.54 (Ph), 130.96 (Ph), 143.81 (Ph), 146.49 (Ph), 167.80(C═O),

IR (neat): 3010 (Ph), 2957, 2928, 2857, 1716 (C═O), 1609, 1458, 1366,1275, 1258, 1180, 1142, 1100, 1071, 1100, 1070 cm⁻¹.

Elemental analysis: calculated (C₂₃H₃₈O₂): C, 79.71%; H, 11.05%. found:C, 79.57%; H, 10.84%.

The synthesized sample was found identical with the reference materialof t-butyl 2,4-dihexylbenzoate which was synthesized separately fromcommercial 4-bromoisophthalic acid in the following manner.

Example 6 t-butyl 2,4-dihexylbenzoate

The same procedure as in Example 5 was repeated except thatp-toluenesulfonylacetylene was replaced by p-toluenesulfinylacetylene.There was obtained t-butyl 2,4-dihexylbenzoate in a 17% yield.

Example 7 t-butyl 2-deuterio-4,6-dihexylbenzoate

The same procedure as in Example 5 was repeated except that heavy waterwas added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained t-butyl 2-deuterio-4, 6-dihexylbenzoate.

¹H NMR: δ 0.87 (t, J=7.5 Hz, 6H, Me), 1.20–1.42 (m, 16H, alkyl H), 1.58(s, 9H, C(CH₃)₃), 2.58 (t, J=7.8 Hz, 2H, PhCH₂), 2.89 (t, J=7.8 Hz, 2H,PhCH₂), 7.01 (s, 2H, Ph-H).

An introduction of 98% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.67 (Ph-H) oft-butyl 2,4-dihexylbenzoate.

Example 8 t-butyl 2,4-dihexyl-6-iodobenzoate

To a diethyl ether solution (1.5 mL) containing t-butyl 2-nonynoate (20mg, 0.095 mmol) and tetra-i-propoxytitanium (0.035 mL, 0.119 mmol) wasadded i-propylmagnesium chloride (1.63 M diethyl ether solution, 0.163mL, 0.266 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution kept at −50° C. was given1-octyne (0.011 mL, 0.076 mmol), and the solution was stirred for 3hours. The solution was given a diethyl ether solution (1 mL) containingpowdery p-toluenesulfonylacetylene (21 mg, 0.114 mmol). The reactionsolution was heated to room temperature.

The reaction solution was stirred at room temperature for 3 hours andthen given a tetrahydrofuran solution (1 mL) containing iodine (72 mg,0.285 mmol). The solution was stirred for 1 hour and then givenhydrochloric acid (1 mol/L) to suspend the reaction. The reactionproduct was extracted with diethyl ether. The organic layer was washedwith an aqueous solution of sodium bicarbonate and sodium thiosulfateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-diethyl ether).There was obtained t-butyl 2,4-dihexyl-6-iodobenzoate (20 mg, 56%) inthe form of colorless oily substance.

¹H NMR: δ 0.80–0.95 (m, 6H, Me), 1.12–1.45 (m, 16H, alkyl H), 1.62 (s,9H, C(CH₃)₃), 2.50 (t, J=7.8 Hz, 2H, PhCH₂), 2.57 (t, J=7.8 Hz, 2H,PhCH₂), 6.95 (d, J=1.5 Hz, 1H, Ph-H), 7.46 (d, J=1.5 Hz, 1H, Ph-H).

¹³C NMR: δ 13.93 (2 peaks), 22.45 (2 peaks), 28.01 (C(CH₃)₃), 28.76,29.22, 31.01, 31.37, 31.53, 31.57, 34.18, 35.14, 82,71 (CO₂C), 91.96(Ph), 129.22 (Ph), 136.47 (Ph), 138.16 (Ph), 140.91 (Ph), 145.46 (Ph),168.52 (C═O).

IR (neat): 3010 (Ph), 2960, 2927, 2857, 1725 (C═O), 1600, 1546, 1458,1391, 1367, 1285, 1260, 1146, 1101, 1070, 847 cm⁻¹.

Example 9 5,7-dihexyl-3-phenylphthalide

To a diethyl ether solution (1.5 mL) containing t-butyl 2-nonynoate (30mg, 0.143 mmol) and tetra-i-propoxytitanium (0.053 mL, 0.178 mmol) wasadded i-propylmagnesium chloride (1.35 M diethyl ether solution, 0.296mL, 0.399 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution kept at −50° C. was given1-octyne (0.017 mL, 0.114 mmol), and the solution was stirred for 3hours. The solution was given a diethyl ether solution (1 mL) containingpowdery p-toluenesulfonylacetylene (31 mg, 0.171 mmol). The reactionsolution was heated to room temperature. The reaction solution wasstirred at room temperature for 3 hours and then cooled to −50° C. Thesolution was given benzaldehyde (0.899 M, diethyl ether solution, 0.190mL, 0.171 mmol). The solution was stirred at −50° C. for 2 hours andthen heated to room temperature. Stirring was continued at roomtemperature for 5 hours.

The solution was given hydrochloric acid (1 mol/L) to suspend thereaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-diethyl ether).There was obtained 5,7-dihexyl-3-phenylphthalide (21 mg, 49%) in theform of colorless oily substance.

¹H NMR: δ 0.80–0.95 (m, 6H, Me), 1.20–1.50 (m, 12H, alkyl H), 1.50–1.76(m, 4H, alkyl H), 2.62 (t, J=7.8 Hz, 2H, PhCH₂), 3.06 (dt, J=2.1, 7.8Hz, 1H, PhCH₂), 3.13 (dt, J=2.1, 7.8 H, 1H, PhCH₂), 6.27 (s, 1H, CO₂CH),6.90 (s, 1H, Ph-H), 7.11 (s, 1H, Ph-H), 7.25–7.31 (m, 2H, Ph-H),7.34–7.42 (m, 3H, Ph-H).

The structure was confirmed (identified) by the fact that a 9% increasein NOE due to irradiate proton at δ 2.62 ppm (PhCH₂) was observed inboth the peak at δ 6.90 ppm (Ph-H) and the peak at δ 7.11 ppm (Ph-H) andthe fact that a 9% increase in NOE due to irradiate proton at δ 3.06 ppm(PhCH₂) and proton at δ 3.13 ppm (PhCH₂) was observed in the peak at δ7.00 ppm (Ph-H).

¹³C NMR: δ 13.88, 13.95, 22.41, 22.49, 28.81, 29.04, 30.89, 30.92,31.06, 31.47, 31.59, 36.18, 81.53 (CO₂C), 119.95 (Ph), 120.32 (Ph),127.10 (o- or m-Ph), 128.93 (m- or o-Ph), 129.10 (Ph), 130.52 (Ph),137.29 (Ph), 144.63 (Ph), 150.32 (Ph), 151.03 (Ph), 170.54 (C═O).

IR (neat): 3070 (Ph), 3038 (Ph), 2960, 2860, 1761 (C═O), 1610, 1458,1301, 1204, 1056, 698 cm⁻¹.

Example 10 t-butyl 2-hexyl-4-(trimethylsilyl)benzoate

The same procedure as in Example 5 was repeated except that 1-octyne wasreplaced by trimethylsilylacetylene. There was obtained t-butyl2-hexyl-4-(trimethylsilyl)benzoate in a 46% yield.

¹H NMR: δ 0.27 (s, 9H, SiMe₃), 0.88, (t, J=7.5 Hz, 3H, Me), 1.15–1.45(m, 8H, alkyl H), 1.59 (s, 9H, C(CH₃)₃), 2.90 (t, J=7.8 Hz, 2H, PhCH₂),7.33 (s, 1H, Ph-H), 7.36 (d, J=7.5 Hz, 1H, Ph-H), 7.69 (d, J=7.5 Hz, 1H,Ph-H).

¹³C NMR: δ −1.43 (SiMe₃), 13.96, 22.55, 28.12 (C(CH₃)₃), 29.42, 31.71,32.02, 34.43, 81.05 (CO₂C), 129.13 (Ph), 130.61 (Ph), 132.43 (Ph),135.80 (Ph), 142.20 (Ph), 144.37 (Ph), 167.99 (C═O).

IR (neat): 3005 (Ph), 2957, 2925, 2860, 1717 (C═O), 1458, 1367, 1250(SiMe₃), 1150, 840 cm⁻¹.

Elemental analysis: calculated (C₂₀H₃₄O₂Si): C, 71.80%; H, 10.24%.found: C, 71.64%; H, 10.53%.

Example 11 t-butyl 2-deuterio-6-hexyl-4-(trimethylsilyl)benzoate

The same procedure as in Example 10 was repeated except that heavy waterwas added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained t-butyl2-deuterio-6-hexyl-4-(trimethylsilyl)benzoate.

¹H NMR: δ 0.27 (s, 9H, SiMe₃), 0.88 (t, J=7.5 Hz, 3H, Me), 1.15–1.45 (m,8H, alkyl H), 1.59 (s, 9H, C(CH₃)₃), 2.90 (t, J=7.8 Hz, 2H, PhCH₂), 7.33(s, 1H, Ph-H), 7.36 (s, 1H, Ph-H).

An introduction of 94% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.69 (Ph-H) oft-butyl 2-hexyl-4-trimethylsilyl)benzoate.

Example 12 4-[2-(benzyloxy)ethyl]-1,2-dibutylbenzene

To a diethyl ether solution (1.5 mL) containing 5-decyne (0.02 mL, 0.111mmol) and tetra-i-propoxytitanium (0.041 mL, 0.139 mmol) was addedi-propyl-magnesium chloride (1.63 M diethyl ether solution, 0.192 mL,0.312 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 2 hours at −50° C. The solution kept at −50° C. wasgiven a diethyl ether solution (1 mL) containing 4-benzyloxy-1-butyne(14 mg, 0.089 mmol) and then stirred for 1 hour. The solution was givena diethyl ether solution (1 mL) containing powderyp-toluenesulfonylacetylene (22 mg, 0.122 mmol). The reaction solutionwas heated to room temperature.

The reaction solution at room temperature was stirred for 3 hours andthen given hydrochloric acid (1 mol/L) to suspend the reaction. Thereaction product was extracted with diethyl ether. The organic layer waswashed with an aqueous solution of sodium bicarbonate and then driedwith anhydrous sodium sulfate. The solvent was distilled away underreduced pressure. There was obtained a crude product in the form of oilysubstance. The crude product was analyzed in detail by ¹H NMR. It wasfound to contain no other isomers. The crude product was purified bysilica gel column chromatography (n-hexane-diethyl ether). There wasobtained 4-[2-(benzyloxy)ethyl]-1,2-dibutylbenzene (17 mg, 57%) in theform of colorless oily substance.

¹H NMR: δ 0.95 (t, J=7.5 Hz, 6H, Me), 1.40 (sextet, J=7.5 Hz, 4H, alkylH), 1.52 (quintet, J=7.5 Hz, 4H, alkyl H), 2.58 (t, J=7.5 Hz, 4H,PhCH₂), 2.89 (t, J=7.5 Hz, 2H, PhCH₂), 3.68 (t, J=7.5 Hz, 2H, CH₂OBn),4.54 (s, 2H, PhCH₂O), 6.98 (d, J=7.5 Hz, 1H, Ph-H), 7.00 (s, 1H, Ph-H),7.06 (d, J=7.5 Hz, 1H, Ph-H), 7.25–7.40 (m, 5H, Ph-H).

¹³C NMR: δ 13.91 (2 peaks), 22.73, 22.80, 31.93, 32.34, 33.46, 33.49,35.89, 71.48 (O—C), 72.91 (O—C), 126.29 (Ph), 127.57 (Ph), 127.71 (o- orm-Ph), 128.41 (m- or o-Ph), 129.19 (Ph), 129.85 (Ph), 136.12 (Ph),138.47 (Ph), 138.60 (Ph), 140.60 (Ph).

IR (neat): 3090 (Ph), 3070 (Ph), 3035 (Ph), 3000 (Ph), 2955 (Ph), 2928,2859, 1497, 1456, 1362, 1205, 1102, 1029, 822, 734, 696 cm⁻¹.

Elemental analysis: calculated (C₂₃H₃₂O): C, 85.13%; H, 9.94%. found: C,85.38%; H, 10.03%.

Example 13

A 72:28 mixture of 1-[2-(benzyloxy)ethyl]-4,5-dibutyl-2-iodobenzene and5-[2-(benzyloxy)ethyl]-1,2-dibutyl-3-iodobenzene.

The same procedure as in Example 12 was repeated except that iodine wasadded for reaction before the addition of hydrochloric acid (1 mol/L).There was obtained a 72:28 mixture of1-[2-(benzyloxy)ethyl]-4,5-dibutyl-2-iodobenzene and5-[2-(benzyloxy)ethyl]-1,2-dibutyl-3-iodobenzene in a 39% yield.

1-[2-(benzyloxy)ethyl]-4,5-dibutyl-2-iodobenzene

(Analyzed from a 72:28 mixture of position isomers.)

¹H NMR: δ 0.80–1.04 (m, 6H, Me), 1.20–1.60 (m, 8H, alkyl H), 2.51 (t,J=7.7 Hz, 4H, PhCH₂), 3.00 (t, J=7.5 Hz, 2H, PhCH₂), 3.66 (t, J=7.5 Hz,2H, CH₂OBn), 4.55 (s, 2H, PhCH₂O), 7.03 (s, 1H, Ph-H), 7.25–7.40 (m, 5H,Ph-H), 7.56 (s, 1H, Ph-H).

The structure was confirmed (identified) by the fact that a 9% increaseand a 13% increase in NOE due to irradiate proton at δ 2.51 ppm (PhCH₂)were observed respectively in the peaks at δ 7.03 ppm (Ph-H) and δ 7.56ppm (Ph-H) and the fact that a 14% increase in NOE due to irradiateproton at δ 3.00 ppm (PhCH₂) was observed in the peak at δ 7.03 ppm(Ph-H).

IR (neat): 3090 (Ph), 3060 (Ph), 3035 (Ph), 2955, 2928, 2859, 1456,1380, 1362, 1205, 1102, 1030, 733, 696 cm⁻¹.

5-[2-(benzyloxy)ethyl]-1,2-dibutyl-3-iodobenzene

¹H NMR: (characteristic peaks only) δ 2.80 (t, J=7.5 Hz, 2H, PhCH₂),3.65 (t, J=7.5 Hz, 2H, CH₂OBn), 4.52 (s, 2H, PhCH₂O), 6.96 (s, 1H,Ph-H), 7.56 (s, 1H, Ph-H).

Example 144-[2-((t-butyl)dimethylsiloxy)ethyl]-2-hexyl-1-(trimethylsilyl) benzene

To a diethyl ether solution (4.5 mL) containing1-trimethylsilyl-1-octyne (60 mg, 0.329 mmol) andtetra-i-propoxytitanium (0.121 mL, 0.411 mmol) was addedi-propylmagnesium chloride (1.46 M diethyl ether solution, 0.630 mL,0.921 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 2 hours at −50° C. The solution kept at −50° C. wasgiven a diethyl ether solution (1 mL) containing4-[(t-butyl)dimethylsiloxy]-1-butyne (48 mg, 0.263 mmol) and thenstirred for 1 hour. The solution was given a diethyl ether solution (1mL) containing powdery p-toluenesulfonylacetylene (71 mg, 0.395 mmol).The reaction solution was heated to room temperature.

The reaction solution (at room temperature) was stirred for 3 hours andthen given hydrochloric acid (1 mol/L) to suspend the reaction. Thereaction product was extracted with diethyl ether. The organic layer waswashed with an aqueous solution of sodium bicarbonate and then driedwith anhydrous sodium sulfate. The solvent was distilled away underreduced pressure. There was obtained a crude product in the form of oilysubstance. The crude product was analyzed in detail by ¹H NMR. It wasfound to contain no other isomers. The crude product was purified bysilica gel column chromatography (n-hexane-diethyl ether). There wasobtained4-[2-((t-butyl)dimethylsiloxy)ethyl]-2-hexyl-1-(trimethylsilyl)benzene(52 mg, 50%) in the form of colorless oily substance.

¹H NMR: δ 0.02 (s, 6H, t-BuSiMe₂), 0.31 (s, 9H, SiMe₃), 0.80–0.95 (m,3H, Me,), 0.89 (s, 9H, C(CH₃)₃), 1.20–1.50 (m, 6H, alkyl H), 1.50–1.68(m, 2H, alkyl H), 2.67 (t, J=8.1 Hz, 2H, PhCH₂), 2.80 (t, J=7.2 Hz, 2H,PhCH₂), 3.81 (t, J=7.2 Hz, 2H, CH₂OTBS), 7.02 (d, J=7.5 Hz, 1H, Ph-H),7.06 (s, 1H, Ph-H), 7.38 (d, J=7.5 Hz, 1H, Ph-H).

¹³C NMR: δ −5.22 (t-BuSiMe₂), 0.37 (SiMe₃), 13.96, 18.24 (C(CH₃)₃),22.53, 25.85 (C(CH₃)₃), 29.60, 31.74, 32.59, 36.30, 39.46, 64.50 (O—C),125.82 (Ph), 129.57 (Ph), 134.64 (Ph), 135.34 (Ph), 140.12 (Ph), 148.93(Ph).

IR (neat): 3045 (Ph), 2960, 2928, 2857, 1604, 1470, 1250 (C—Si), 1098,837, 775 cm⁻¹.

Elemental analysis: calculated (C₂₃H₄₄OSi₂): C, 70.33%; H, 11.29%.found: C, 70.54%; H, 11.58%.

Example 15

A 74:26 mixture of1-[2-((t-butyl)dimethylsiloxy)-ethyl]-5-hexyl-2-iodo-4-(trimethylsilyl)benzeneand5-[2-((t-butyl)dimethylsiloxy)ethyl]-1-hexyl-3-iodo-2-(trimethylsilyl)benzene

The same procedure as in Example 14 was repeated except that iodine wasadded for reaction before the addition of hydrochloric acid (1 mol/L).There was obtained a 74:26 mixture of1-[2-((t-butyl)dimethylsiloxy)ethyl]-5-hexyl-2-iodo-4-(trimethylsilyl)benzeneand5-[2-((t-butyl)dimethylsiloxy)ethyl]-1-hexyl-3-iodo-2-(trimethylsilyl)benzenein a 37% yield.

1-[2-((t-butyl)dimethylsiloxy)ethyl]-5-hexyl-2-iodo-4-(trimethylsilyl)benzene

(Analyzed from a 74:26 mixture of position isomers.)

¹H NMR: δ 0.01 (s, 6H, t-BuSiMe₂), 0.29 (s, 9H, SiMe₃), 0.80–0.95 (m,3H, Me), 0.87 (s, 9H, C(CH₃)₃), 1.20–1.50 (m, 6H, alkyl H), 1.60–1.72(m, 2H, alkyl H), 2.60 (t, J=8.1 Hz, 2H, PhCH₂), 2.91 (t, J=7.2 Hz, 2HPhCH₂), 3.79 (t, J=7.2 Hz, 2H CH₂OTBS), 7.09, (s, 1H, Ph-H), 7.80 (s,1H, Ph-H).

The structure was confirmed (identified) by the fact that a 12% increasein NOE due to irradiate proton at δ 0.01 ppm (SiMe₃) was observed in thepeak at δ 7.80 ppm (Ph-H).

IR (neat): 3038 (Ph), 2954, 2927, 2856, 1591, 1524, 1463, 1379, 1360,1250 (Si—C), 1098, 1006, 909, 837, 776, 734 cm⁻¹.

5-[2-((t-butyl)dimethylsiloxy)ethyl]-1-hexyl-3-iodo-2-(trimethylsilyl)benzene

¹H NMR: (characteristic peaks only) δ 0.01 (s, 6H, t-BuSiMe₂), 0.53 (s,9H, SiMe₃), 2.66 (t, J=8.1 Hz, 2H, PhCH₂), 2.67 (t, J=6.6 Hz, 2H,PhCH₂), 3.77 (t, J=6.6 Hz, 2H, CH₂OTBS), 6.97 (d, J=1.5 Hz, 1H, Ph-H),7.68 (d, J=1.5 Hz, 1H, Ph-H).

Example 16 2,3-bis(cyclohexyloxy)-1,4-bis(trimethylsilyl)benzene

To a diethyl ether solution (1.5 mL) containingcyclohexyl(timethylsilyl)ethynyl ether (30 mg, 0.145 mmol) andtetra-i-propoxytitanium (0.027 mL, 0.091 mmol) was addedi-propylmagnesium chloride (1.42 M diethyl ether solution, 0.144 mL,0.203 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into dark yellowish. The solutionwas kept stirred for 4 hours at −50° C. The solution kept at −50° C. wasgiven a diethyl ether solution (1 mL) containingp-toluenesulfonylacetylene in powder form (16 mg, 0.087 mmol).

The reaction solution was heated to room temperature and was stirred for3 hours. The solution was given hydrochloric acid (1 mol/L) to suspendthe reaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-diethyl ether).There was obtained 2,3-bis(cyclohexyloxy)-1,4-bis(trimethylsilyl)benzene(18 mg, 56%) in the form of colorless oily substance.

¹H NMR: δ 0.28 (s, 18H, SiMe₃), 1.08–1.40 (m, 10H, cyclohexyl H), 1.60(symmetric m, 2H, cyclohexyl H), 1.75 (symmetric m, 4H, cyclohexyl H),1.86 (symmetric m, 4H, cyclohexyl H), 4.30 (tt, J=3.9, 10.5 Hz, 2H,O—CH, 7.05 (s, 2H, Ph-H).

¹³C NMR: δ 0.06 (SiMe₃), 24.82, 25.72, 32.69, 78.26 (O—C), 128.72 (Ph),135.61 (Ph), 153.35 (Ph).

IR (neat): 3060 (Ph), 2933, 2857, 1590, 1451, 1363, 1344, 1245, 1221,1196, 1177, 1127, 1043, 1019, 966, 887, 836, 758 cm⁻¹.

Example 172,3-bis(cyclohexyloxy)-5-deuterio-1,4-bis(trimethylsilyl)benzene

The same procedure as in Example 16 was repeated except that heavy waterwas added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained2,3-bis(cyclohexyloxy)-5-deuterio-1,4-bis(trimethyl-silyl)benzene.

¹H NMR: δ 0.28 (s, 18H, SiMe₃) 1.08–1.40 (m, 10H, cyclohexyl H), 1.60(symmetric m, 2H, cyclohexyl H), 1.75 (symmetric m, 4H, cyclohexyl H),1.86 (symmetric m, 4H, cyclohexyl H), 4.30 (tt, J=3.9, 10.5 Hz, 2H,0-CH), 7.05 (s, 1H, Ph-H).

An introduction of 98% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.05 (Ph-H) of2,3-bis(cyclohexyloxy)-1,4-bis(trimethylsilyl)benzene.

Example 18 2,2-bis[(benzyloxy)methyl]-4,7-bis(trimethylsilyl)indan

To a diethyl ether solution (4.5 mL) containing4,4-bis[(benzyloxy)methyl]-1,7-bis(trimethylsilyl)-1,6-heptadiyne (50mg, 0.105 mmol) and tetra-i-propoxytitanium (0.039 mL, 0.131 mmol) wasadded i-propylmagnesium chloride (1.49 M diethyl ether solution, 0.197mL, 0.293 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into dark yellowish. The solutionwas kept stirred for 4 hours at −50° C. The solution (kept at −50° C.)was given a diethyl ether solution (1 mL) containingp-toluenesulfonylacetylene in powder form (23 mg, 0.126 mmol).

The reaction solution was heated to room temperature and was stirred for3 hours. The solution was given hydrochloric acid (1 mol/L) to suspendthe reaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was purified by silica gelcolumn chromatography (n-hexane-diethyl ether). There was obtained2,2-bis[(benzyloxy)methyl]-4,7-bis(trimethylsilyl)indan (39 mg, 74%) inthe form of colorless oily substance.

¹H NMR: δ 0.28 (s, 18H, SiMe₃), 2.90 (s, 4H, PhCH₂), 3.52 (s, 4H,CH₂OBn), 4.53 (s, 4H, PhCH₂O), 7.22–7.35 (m, 12H, Ph-H).

¹³C NMR: δ −0.97 (SiMe₃), 39.65, 47.69, 73.22, 73.44, 127.46 (Ph),127.55 (o- or m-Ph), 128.36 (m- or o-Ph), 131.29 (Ph), 136.87 (Ph),138.98 (Ph), 146.75 (Ph).

IR (neat): 3090 (Ph), 3060 (Ph), 3033 (Ph), 2953, 2895, 2852, 1496,1453, 1359, 1249 (SiMe₃), 1198, 1100, 1028, 892, 836, 751, 696 cm⁻¹.

Elemental analysis: calculated (C₃₁H₄₂O₂Si₂): C, 74.05%; H, 8.42%.found: C, 73.89%; H, 8.35%.

Example 19 N-benzyl-4,7-bis(trimethylsilyl)-1-isoindolinone

To a diethyl ether solution (1.5 mL) containingN-benzyl-N-[3-(trimethylsilyl)-2-propinyl]-3-(trimethylsilyl)-2-propinamide(30 mg, 0.088 mmol) and tetra-i-propoxytitanium (0.039 mL, 0.132 mmol)was added i-propylmagnesium chloride (1.48 M diethyl ether solution,0.179 mL, 0.263 mmol) at −78° C. under an argon stream. There wasobtained a homogenous yellowish solution. The solution was slowly heatedto −30° C. over 30 minutes. The solution turned into reddish. Thesolution was kept stirred for 4 hours at −30° C. The solution (kept at−30° C.) was given a diethyl ether solution (1 mL) containingp-toluenesulfonylacetylene (19 mg, 0.105 mmol) in powder form.

The reaction solution was heated to room temperature and was stirred for3 hours. The solution was given hydrochloric acid (1 mol/L) to suspendthe reaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was purified by silica gelcolumn chromatography (n-hexane-ethyl acetate). There was obtainedN-benzyl-4,7-bis(trimethylsilyl)-1-isoindolinone (24 mg, 88%) in theform of colorless oily substance.

¹H NMR: δ 0.27 (s, 9H, SiMe₃), 0.44 (s, 9H, SiMe₃), 4.29 (s, 2H,PhCH₂N), 4.81 (s, 2H, PhCH₂N), 7.27–7.39 (m, 5H, Ph-H), 7.59 (d, J=7.2Hz, 1H, Ph-H), 7.63 (d, J=7.2 Hz, 1H, Ph-H).

¹³C NMR: δ −0.96 (SiMe₃), −0.61 (SiMe₃), 46.31, 50.49, 127.62 (Ph),128.09 (o- or m-Ph), 128.83 (m- or o-Ph), 133.70 (Ph), 135.09 (Ph),135.84 (Ph), 136.09 (Ph), 137.36 (Ph), 139.75 (Ph), 146.25 (Ph), 169.59(C═O).

IR (neat): 3050 (Ph), 3030 (Ph), 2953, 1688 (C═O), 1640, 1540, 1496,1452, 1410, 1358, 1320, 1293, 1250 (SiMe₃), 1193, 1028, 944, 919, 840,751, 696 cm⁻¹.

Elemental analysis: calculated (C₂₁H₂₉NOSi): C, 68.61%; H, 7.95%; N,3.81%. found: C, 68.40%; H, 7.87%; N, 3.75%.

Example 20 5-(t-butoxycarbonyl)-6-hexylindan

(1,6-heptadiynyl p-tolylsulfone)

First, 1,6-heptadiynyl p-tolylsulfone as a starting material wassynthesized according to the following scheme.

¹H NMR: δ 1.76 (quintet, J=6.9 Hz, 2H, alkyl H), 1.96 (t, J=2.4 Hz, 1H,C≡CH), 2.25 (dt, J=2.4, 6.9 Hz, 2H, CH₂C≡CH), 2.46 (s, 3H, PhMe), 2.51(t, J=6.9 Hz, 2H, CH₂C≡CSO₂Tol), 7.37 (d, J=8.4 Hz, 2H, Ph-H), 7.87 (d,J=8.4 Hz, 2H, Ph-H).

¹³C NMR: δ 17.65, 17.94, 21.80, 25.91, 69.77 (C≡C), 78.81 (C≡C), 82.18(C≡C), 95.71 (C≡C), 127.21 (o- or m-Ph), 129.79 (m- or o-Ph), 138.78(p-Ph), 145.08 (ipso-Ph).

IR (neat): 3289 (Ph), 3058 (Ph), 2940, 2201 (C≡C), 1595, 1431, 1327(S═O), 1158 (S═O), 1089, 1048, 814 cm⁻¹.

Elemental analysis: calculated (C₁₄H₁₄O₂S): C, 68.26%; H, 5.73%. found:C, 67.93%; H, 5.53%.

To a diethyl ether solution (1.5 mL) containing t-butyl 2-nonyonate (20mg, 0.095 mmol) and tetra-i-propoxytitanium (0.035 mL, 0.119 mmol) wasadded i-propylmagnesium chloride (1.48 M diethyl ether solution, 0.180mL, 0.267 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution (kept at −50° C.) was givena diethyl ether solution (1 mL) containing 1,6-heptadinyl p-tolylsulfone(19 mg, 0.076 mmol) and the solution was stirred at −50° C. for 3 hours.

The reaction solution was heated to room temperature and was stirred for3 hours. The solution was given hydrochloric acid (1 mol/L) to suspendthe reaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was purified by silica gelcolumn chromatography (n-hexane-diethyl ether). There was obtained5-(t-butoxycarbonyl)-6-hexylindan (17 mg, 74%) in the form of colorlessoily substance.

¹H NMR: δ 0.88 (t, J=6.9 Hz, 3H, Me), 1.20–1.55 (m, 8H, alkyl H), 1.58(s, 9H, C(CH₃)₃), 2.06 (quintet, J=7.2 Hz, 2H, cyclopentyl H), 2.86 (t,J=7.2 Hz, 2H, PhCH₂), 2.88 (t, J=7.2 Hz, 4H, PhCH₂), 7.06 (s, 1H, Ph-H),7.58 (s, 1H, Ph-H).

¹³C NMR: δ 13.98, 22.52, 25.35, 28.15 (C(CH₃)₃), 29.41, 31.75, 32.14,32.20, 32.76, 34.32, 80.70 (CO₂C), 125.91 (Ph), 126.56 (Ph), 130.04(Ph), 141.65 (Ph), 141.75 (Ph), 147.89 (Ph), 168.27 (C═O).

IR (neat): 3005 (Ph), 2960, 2927, 2845, 1716 (C═O), 1458, 1390, 1366,1278, 1255, 1167, 1118, 1022, 885, 856, 800 cm⁻¹.

Elemental analysis: calculated (C₂₀H₃₀O₂): C, 79.42%; H, 10.00%. found:C, 79.19%; H, 10.10%.

Example 21 5-(t-butoxycarbonyl)-4-deuterio-6-hexylindan

The same procedure as in Example 20 was repeated except that heavy waterwas added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained 5-(t-butoxycarbonyl)-4-deuterio-6-hexylindan.

¹H NMR: δ 0.88 (t, J=6.9 Hz, 3H, Me), 1.20–1.55 (m, 8H, alkyl H), 1.58(s, 9H, C(CH₃)₃), 2.06 (quintet, J=7.2 Hz, 2H, cyclopentyl H), 2.86 (t,J=7.2 Hz, 2H, PhCH₂), 2.88 (t, J=7.2 Hz, 4H, PhCH₂), 7.06 (s, 1H, Ph-H).

An introduction of 91% deuterium was indicated by the degree ofdisappearance of the proton peak corresponding to δ 7.58 (Ph-H) of5-(t-butoxycarbonyl)-6-hexylindan.

Examples 22 and 23

The same procedure as in Example 20 was repeated to give the followingcompounds except that the acetylene compound and diyne compound werereplaced.

TABLE 1 Example R¹ R² Z Yield (%) 22 CO₂Et Me CH₂C(CH₂OBn)₂CH₂ 60 23CONEt₂ C₆H₁₃ (CH₂)₃ 73

Example 24 3,4-dibutylphenyl p-tolylsulfoxide

To a diethyl ether solution (1.5 mL) containing 5-decyne (0.020 mL,0.111 mmol) and tetra-i-propoxytitanium (0.041 mL, 0.139 mmol) was addedi-propylmagnesium chloride (1.35 M diethyl ether solution, 0.231 mL,0.312 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 2 hours at −50° C. The solution (kept at −50° C.) wasgiven a diethyl ether solution (1 mL) containingp-toluenesulfinylacetylene (37 mg, 0.223 mmol) and the solution wasstirred at −50° C. for 1 hour.

The reaction solution was heated to −20° C. and then stirred for 7hours. The solution was given hydrochloric acid (1 mol/L) to suspend thereaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product was analyzed in detail by ¹HNMR. It was found to contain no other isomers. The crude product waspurified by silica gel column chromatography (n-hexane-ethyl acetate).There was obtained 3,4-dibutylphenyl p-tolylsulfoxide (18 mg, 50%) inthe form of colorless oily substance.

¹H NMR: δ 0.91 (t, J=7.2 Hz, 3H,. Me), 0.92 (t, J=7.2 Hz, 3H, Me), 1.36(sextet, J=7.2 Hz, 4H, alkyl H), 1.45–1.60 (m, 4H, alkyl H), 2.35 (s,3H, PhMe), 2.58 (t, J=7.2 Hz, 2H, PhCH₂), 2.61 (t, J=7.2 Hz, 2H, PhCH₂),7.19 (d, J=8.1 Hz, 1H, Ph-H), 7.25 (d, J=8.1 Hz, 2H, Ph-H), 7.30 (dd,J=1.8, 8.1 Hz, 1H, Ph-H), 7.43 (d, J=1.8 Hz, 1H, Ph-H), 7.52 (d, J=8.1Hz, 2H, Ph-H).

¹³C NMR: δ 13.81 (2 peaks), 21.27, 22.58, 22.64, 32.19, 32.27, 32.96,33.05, 122.34 (Ph), 125.00 (o- or m-Ph), 125.44 (Ph), 129.98 (m- oro-Ph), 130.08 (Ph), 141.37 (Ph), 142.12 (Ph), 142.64 (Ph), 142.84 (Ph),144.20 (Ph).

IR (neat): 3033 (Ph), 2959, 2925, 2862, 1735, 1720, 1655, 1595, 1458,1400, 1380, 1305, 1090, 1048 (S═O), 970, 808 cm⁻¹.

Example 25 t-butyl 5-hexyl-4-methyl-2-(trimethylsilyl)benzoate

To a diethyl ether solution (3 mL) containing t-butyl3-(trimethylsilyl)-2-propinoate (50 mg, 0.252 mmol) andtetra-i-propoxytitanium (0.093 mL, 0.315 mmol) was addedi-propylmagnesium chloride (1.47 M diethyl ether solution, 0.480 mL,0.706 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution (kept at −50° C.) was given1-octyne (0.030 mL, 0.202 mmol), and the solution was stirred for 3hours.

The solution was given propargylbromide (0.028 mL, 0.378 mmol). Thereaction solution was heated to room temperature and stirred for 4 hoursat room temperature. The solution was given hydrochloric acid (1 mol/L)to suspend the reaction. The reaction product was extracted with diethylether. The organic layer was washed with an aqueous solution of sodiumbicarbonate and then dried with anhydrous sodium sulfate. The solventwas distilled away under reduced pressure. There was obtained a crudeproduct in the form of oily substance. The crude product underwentpreparative silica gel thin-layer chromatography (n-hexane-diethylether). There was obtained t-butyl5-hexyl-4-methyl-2-(trimethylsilyl)benzoate (37 mg, 52%) in the form ofcolorless oily substance.

Examples 26 and 27

The same procedure as in Example 25 was repeated to give the followingcompounds except that the acetylene compound was replaced.

TABLE 2 Exam- ple R¹ R² R⁴ A B 26 SiMe₃ CO₂t-Bu

— 53% 27 SiMe₃ C₆H₁₃ (CH₂)₂OBn 35% —

Example 28

The same procedure as in Example 27 was repeated except that heavy waterwas added for reaction before the addition of hydrochloric acid (1mol/L). There was obtained a compound represented by the formula belowin which deuteration took place at the benzyl position. Incidentally,the ratio of introduction of deuterium was quantitative.

Example 292,2-bis[(benzyloxy)methyl]-5-methyl-4,7-bis(trimethylsilyl)indan

To a diethyl ether solution (2 mL) containing4,4-bis[(benzyloxy)methyl]-1,7-bis(trimethylsilyl)-1,6-heptadiyne (50mg, 0.104 mmol) and tetra-i-propoxytitanium (0.039 mL, 0.131 mmol) wasadded i-propylmagnesium chloride (1.53 M diethyl ether solution, 0.185mL, 0.282 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution was kept stirred for 4 hours at −50° C.The solution (kept at −50° C.) was given propargylbromide (0.012 mL,0.157 mmol).

The reaction solution was heated to room temperature and stirred for 4hours. The solution was given hydrochloric acid (1 mol/L) to suspend thereaction. The reaction product was extracted with diethyl ether. Theorganic layer was washed with an aqueous solution of sodium bicarbonateand then dried with anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. There was obtained a crude product in theform of oily substance. The crude product underwent preparative silicagel thin-layer chromatography (n-hexane-diethyl ether). There wasobtained2,2-bis[(benzyloxy)methyl]-5-methyl-4,7-bis(trimethylsilyl)indan (40 mg,73%) in the form of colorless oily substance.

Examples 30 to 34

The same procedure as in Example 29 was repeated to give the followingcompounds except that the acetylene compound or electrophilic reagentwas replaced.

TABLE 3 Electrophilic Yield Example R⁵ X⁶ reagent Q (%) 30 H Cl H⁺ CH₃60 31 Me Br H⁺ CH₃ 31 32 H Br I₂

72 33 H Br O₂

43 34 H Br

42

Example 35 N,N-diethyl-3-hexyl-5-phenyl-2-picolinamide

To a diethyl ether solution (1.5 mL) containingN,N-diethyl-2-nonyneamide (48 mg, 0.229 mmol) andtetra-i-propoxytitanium (0.084 mL, 0.285 mmol) was addedi-propylmagnesium chloride (1.53 M diethyl ether solution, 0.418 mL,0.637 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into reddish. The solution was keptstirred for 5 hours at −50° C. The solution (kept at −50° C.) was givenethynylbenzene (0.020 mL, 0.182 mmol). The solution was stirred for 3hours.

Then, the solution was given p-toluenesulfonylcyanide (49 mg, 0.273mmol) in powder form. The solution was stirred at −50° C. for 3 hoursand then given water to suspend the reaction. The solution was givenanhydrous sodium sulfate. Precipitates were filtered off through Celite,and the solvent was distilled away under reduced pressure. There wasobtained a crude product in the form of oily substance. The crudeproduct was purified by silica gel column chromatography (n-hexane-ethylacetate). There was obtained N,N-diethyl-3-hexyl-5-phenyl-2-picolinamide(43 mg, 70%). in the form of colorless oily substance.

Example 36 N,N-diethyl-3-hexyl-5-phenyl-6-iodo-2-picolinamide

The same procedure as in Example 35 was repeated except that iodine wasadded before water was added to suspend the reaction. There was obtainedN,N-diethyl-3-hexyl-5-phenyl-6-iodo-2-picolinamide in a 70% yield.

Examples 37 to 40

The same procedure as in Example 35 was repeated to give the followingcompounds except that the acetylene compound was replaced and thereaction temperature (for reaction of p-toluenesulfonecyanide) waschanged.

TABLE 4 Reaction temperature Example R¹ R² R⁴ (° C.) A B 37 CONEt₂ C₆H₁₃C₆H₁₃ −50 — 63% 38 CONEt₂ C₆H₁₃ SiMe₃ −50 — 55% 39 CO₂t—Bu C₆H₁₃ C₆H₁₃−50 — 28% 40 CO₂t—Bu C₆H₁₃ C₆H₁₃ −10 — 50%

Example 41 2-[2-(benzyloxy)ethyl]-4,5-dibutylpyridine

To a diethyl ether solution (1.5 mL) containing 5-decyne (0.020 mL,0.111 mmol) and tetra-i-propoxytitanium (0.41 mL, 0.139 mmol) was addedi-propylmagnesium chloride (1.36 M diethyl ether solution, 0.229 mL,0.312 mmol) at −78° C. under an argon stream. There was obtained ahomogenous yellowish solution. The solution was slowly heated to −50° C.over 30 minutes. The solution turned into blackish. The solution waskept stirred for 3 hours at −50° C. The solution (kept at −50° C.) wasgiven a diethyl ether solution (1 mL) of 4-benzyloxy-1-butyne (14 mg,0.089 mmol). The solution was stirred for 2 hours.

Then, the solution was given a diethyl ether solution (1 mL) containingp-toluenesulfonylcyanide in powder form (24 mg, 0.134 mmol). Thereaction solution was heated to −10° C. The solution was stirred at −10°C. for 3 hours and then given water to suspend the reaction. Thesolution was given anhydrous sodium sulfate. Precipitates were filteredoff through Celite, and the solvent was distilled away under reducedpressure. There was obtained a crude product in the form of oilysubstance. The crude product was purified by silica gel columnchromatography (n-hexane-ethyl acetate). There was obtained2-[2-(benzyloxy)ethyl]-4,5-dibutyl-pyridine (16 mg, 55%) in the form ofcolorless oily substance.

The present invention permits efficient production of an organotitaniumcompound capable of regioselectively converting a substituted acetylenecompound into polysubstituted benzene or polysubstituted pyridine. Thepresent invention also permits efficient production of a variety ofpolysubstituted benzene and polysubstituted pyridine useful forpharmaceuticals and agricultural chemicals and intermediates thereof byvarious addition reactions on the titanium compound.

1. A process for producing an organotitanium compound which comprisesreacting an acetylene compound represented by the formula (8) below inthe presence of a titanium compound represented by the formula (2) belowand a Grignard reagent represented by the formula (3) below with acompound represented by the formula (5) below, thereby giving saidtitanium compound represented by the formula (9) and/or (10) below

where R¹ denotes a C₁₋₂₀ alkyl group {which may be substituted with aC₁₋₆ alkoxy group (which may be substituted with a phenyl group) orOSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ denote mutually independently a C₁₋₆alkyl group or phenyl group)}, C₃₋₂₀ alkenyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkyaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² denote mutuallyindependently a halogen atom, C₁₋₆ alkyl group, or phenyl group); R⁴denotes a hydrogen atom, C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, and R¹² are defined as above);and Y denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷ {where Z¹, Z³, Z⁴, Z⁵, and Z⁷denote mutually independently C═O or CR¹⁴R¹⁵ (where R¹⁴ and R¹⁵ denotemutually independently a hydrogen atom or C₁₋₆ alkyl group (which may besubstituted with a C₁₋₆ alkoxy group (which may be substituted with aphenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove))>, Z² and Z⁶ denote mutually independently O, S, C═O, NR¹⁶ <whereR¹⁶ denotes a C₁₋₆ alkyl group (which may be substituted with a C₁₋₆alkoxy group (which may be substituted with a C₁₋₆ alkoxy group (whichmay be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, andR⁹ are defined as above))>, or CR^(14′)R^(15′) (where R^(14′) andR^(15′) denote mutually independently a hydrogen atom or C₁₋₆ alkylgroup (which may be substituted with a C₁₋₆ alkoxy group (which may besubstituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ aredefined as above))>}TiX¹X²X³X⁴  (2) where X¹, X², X³, and X⁴ denote mutually independently ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group), or a naphthyl group)}, phenoxy group (which maybe substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), or naphthoxy groupRMgX⁵  (3) where R denotes a C₂₋₈ alkyl group having a hydrogen atom atthe β position, and X⁵ denotes a halogen atom

where R⁵ denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group(which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), Z denotes CR′ (where R′ denotes ahydrogen atom or C₁₋₂₀ alkyl group) or a nitrogen atom; X⁶ denotes ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, and phenyl group), or naphthyl group}, phenoxy group (which maybe substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), naphthoxy group, SO_(n)R⁶ {where R⁶ denotes a C₁₋₆ alkyl groupor phenyl group (which may be substituted with a halogen atom or C₁₋₆alkyl group) and n denotes 1 or 2}, OSO₂R⁶ (where R⁶ is defined asabove), or OP(O)(OR¹³)₂ group (where R¹³ denotes a C₁₋₆ alkyl group);and m denotes 0 or 1

where R¹, R⁴, R⁵, Y, Z, X⁶, and m are defined as above; and X^(p) andX^(q) denote any of X¹˜X⁴ (which are defined as above).
 2. A process forproducing an organotitanium compound which comprises reacting anacetylene compound represented by the formula (1) below in the presenceof a titanium compound represented by the formula (2) below and aGrignard reagent represented by the formula (3) below with a compoundrepresented by the formula (11) below, thereby giving said titaniumcompound represented by the formula (12) below

where R¹ and R² denote mutually independently a C₁₋₂₀ alkyl group {whichmay be substituted with a C₁₋₆ alkoxy group (which may be substitutedwith a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ denote mutuallyindependently a C₁₋₆ alkyl group or phenyl group)}, C₃₋₂₀ alkenyl group,C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonylgroup, di-C₁₋₆-alkyaminocarbonyl group, phenyl group (which may besubstituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group), furyl group, amino group, SiR⁷R⁸R⁹(where R⁷, R⁸, and R⁹ are defined as above), or SnR¹⁰R¹¹R¹² (where R¹⁰,R¹¹, and R¹² denote mutually independently a halogen atom, C₁₋₆ alkylgroup, or phenyl group)TiX¹X²X³X⁴  (2) where X¹, X², X³, and X⁴ denote mutually independently ahalogen atom, C₁₋₆ alkoxy group {which may be substituted with a phenylgroup (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxygroup, or phenyl group), or a naphthyl group}, phenoxy group (which maybe substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, or phenylgroup), or naphthoxy group)RMgX⁵  (3) where R denotes a C₂₋₈ alkyl group having a hydrogen atom atthe β position, and X⁵ denotes a halogen atom

where R³ denotes a hydrogen atom, C₁₋₂₀ alkyl group, C₁₋₆ alkoxy group,C₁₋₆ alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group,di-C₁₋₆-alkylaminocarbonyl group, phenyl group (which may be substitutedwith a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆ alkoxycarbonyl group,C₁₋₆ alkylaminocarbonyl group, or di-C₁₋₆-alkylaminocarbonyl group),furyl group, amino group, SiR⁷R⁸R⁹ (R⁷, R⁸, and R⁹ are defined asabove), or SnR¹⁰R¹¹R¹² (where R¹⁰, R¹¹, R¹² are defined as above); R⁵denotes a hydrogen atom, C₁₋₂₀ alkyl group, or phenyl group (which maybe substituted with a C₁₋₆ alkyl group, C₁₋₆ alkoxy group, C₁₋₆alkoxycarbonyl group, C₁₋₆ alkylaminocarbonyl group, ordi-C₁₋₆-alkylaminocarbonyl group); Y′ denotes Z¹-Z²-Z³ or Z⁴-Z⁵-Z⁶-Z⁷{where Z¹, Z³, Z⁴, Z⁵, and Z⁷ denote mutually independently C═O orCR¹⁴R¹⁵ <where R¹⁴ and R¹⁵ denote mutually independently a hydrogen atomor C₁₋₆ alkyl group (which may be substituted with a C₁₋₆ alkoxy group(which may be substituted with a phenyl group) or OSiR⁷R⁸R⁹ (where R⁷,R⁸, and R⁹ are defined as above))>, Z² and Z⁶ denote mutuallyindependently O, S, C═O, NR¹⁶ (where R¹⁶ denotes a C₁₋₆ alkyl group(which may be substituted with C₁₋₆ alkoxy group (which may besubstituted with a phenyl group)) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ aredefined as above)>, or CR^(14′)R^(15′) <where R^(14′) and R^(15′) denotemutually independently a hydrogen atom, C₁₋₆ alkyl group (which may besubstituted with a C₁₋₆ alkoxy group (which may be substituted with aphenyl group) or OSiR⁷R⁸R⁹ (where R⁷, R⁸, and R⁹ are defined asabove))>}; X⁶ denotes a halogen atom, C₁₋₆ alkoxy group {which may besubstituted with a phenyl group (which may be substituted with a C₁₋₆alkyl group, C₁₋₆ alkoxy group, or phenyl group), or naphthyl group},phenoxy group (which may be substituted with a C₁₋₆ alkyl group, C₁₋₆alkoxy group, or phenyl group), naphthoxy group, SO_(n)R⁶ {where R⁶denotes a C₁₋₆ alkyl group or phenyl group (which may be substitutedwith a halogen atom or C₁₋₆ alkyl group), and n denotes 1 or 2}, OSO₂R⁶(where R⁶ is defined as above), or OP(O) (OR¹³)₂ group (where R¹³denotes a C₁₋₆ alkyl group); and m denotes 0 or 1

where R¹ to R³, R⁵, Y′, X⁶, and m are defined as above; and X^(p) andX^(q) denote any of X¹˜X⁴ (which are defined as above).
 3. A process forproducing an organotitanium compound as defined in claim 1 or 2, whereinthe titanium compound is tetra-i-propoxytitanium.
 4. A process forproducing an organotitanium compound as defined in claim 1 or 2, whereinthe Grignard reagent is an i-propyl Grignard reagent.
 5. A process foraddition reaction which comprises adding to the organotitanium compoundobtained by the process defined in claim 1 or 2 a compound having analdehyde group, ketone group, imino group, aliphatic double bond,aliphatic triple bond, acyl group or ester group or an electrophilicreagent of water, heavy water, iodine or oxygen, and performing additionreaction on the organotitanium compound to produce a polysubstitutedfused bicyclic compound containing a benezene or a pyridine ring as aone of the fused rings.